Selected renal cell populations, characteristics and uses thereof

Abstract

Methods of identifying an enriched heterogeneous renal cell population having therapeutic potential, enriched heterogeneous renal cell populations having therapeutic potential and uses for same.

Description

SELECTED RENAL CELL POPULATIONS, CHARACTERISTICS AND USESTHEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 512,541, filed on July 7, 2023, and U.S. Provisional Patent Application Serial No. 63 / 589,934, filed on October 12, 2023. The disclosures of the above-referenced applications are herein expressly incorporated by reference it their entireties, including any drawings.BACKGROUND

[0002] Chronic kidney disease (CKD) is reaching, or has reached, pandemic proportions (Thurlow JS, et al., Am J Nephrol 52(2021):98-107; Murphy D, et al., Intern Med 65(2016):473-481; Hill NR, et al., PLoS One l l:e0158765. doi:10.1371 / journal. pone.0158765). Prevalence data from the U.S. to Europe show that approximately 10% of the general population has stage 1-3 CKD (ERA, 2009; USRDS, 2011; Jha et al., Lancet. 382(2013):260-72). CKD has increased >33% between 1996 and 2006 in the US alone (U.S. Renal Data System. Costs of CKD and ESRD. Minneapolis, MN, 2007). Meanwhile, management of CKD remains a challenge for nephrologists. Most standard-of- care treatments for CKD are small molecules targeting biochemical pathways in the kidney to affect single or related co-morbidities. However, these treatments do not affect the underlying CKD kidney’s glomerular and tubulointerstitial dysfunction. Ultimately, in patients that progress to end stage renal disease (ESRD), renal replacement therapy (RRT; dialysis or transplantation) is required for survival. There remains an unmet need for a therapeutic modality that directly addresses the diseased kidney’s tissue biology. Such a therapeutic modality can potentially arrest or even reverse CKD progression and mitigate or avert the need for RRT.

[0003] Selected renal cells (SRC), a heterogeneous renal cell population enriched for renal epithelial cells, are being advanced as autologous cell-based therapy for treatment of CKD (Stavas J, et al., A J Nephrol 53(2022):50-58.; Stavas J, et al., KI Reports, in press). Derived from the donor kidney, SRC is an admixture principally of proximal tubular epithelial cells (Presnell SC, et al, Tissue Eng Part C Methods 17(2011 ) :261 -73) . Results from a Phase II clinical trial in a diabetic kidney disease cohort suggested that SRC administration is safe and is accompanied by improvement in renal function (Stavas J, et al., KI Reports, in press).

[0004] There is a need in the art to identify heterogenous renal cell populations, such as SRCs, that have potential therapeutic activity, e.g., based on their capacity to drive renal tubule formation.BRIEF SUMMARY

[0005] The present disclosure relates generally to a method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential. In the method, it is determined whether cells of the enriched heterogeneous renal cell population express at least one cell adhesion marker. The at least one cell adhesion marker includes, or is one or more of: intercellular adhesion molecule 5 (ICAM5), melanoma cell adhesion molecule (MCAM), contactin associated protein 1 (CNTNAP1), or matrix metallopeptidase 2 (MMP2). The enriched heterogeneous renal cell population is identified as having therapeutic potential if cells of the enriched heterogeneous renal cell population are determined to express the at least one cell adhesion marker.

[0006] The present disclosure describes yet another method of identifying an enriched heterogeneous renal cell population as having therapeutic potential. In the method, expression of transforming growth factor beta 2 (TGF|32) by cells of the enriched heterogeneous renal cell population is determined. The enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that: (i) greater than about 50% of cells of the enriched heterogeneous renal cell population express TGF[32; and / or (ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 1.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.BRIEF DESCRIPTION OF FIGURES

[0007] FIG. 1 Uniform manifold approximation and projection (UMAP) to show SRC population cells that express cdhl . Pink / darker grey dots represent cells that express cdhl . Light grey dots represent cells that do not express cdhl.

[0008] FIG. 2: Shows an interactome, derived from gene ontology and visualized using miRNet, formed by cell-cell adhesion markers (CDH1, CNTNAP1, PECAM1, ICAM5, MCAM, COL11A1 and MMP2) expressed by human SRCs.

[0009] FIG. 3: Provides gene ontology mapping confirming that hsa-miR-145 and hsa-miR- 199a-5p regulate tgf / 32 together with renal cell epithelial markers (CDH1, SLC38A2, SLC8A1) in SRCs.

[0010] FIG. 4: UMAP to show SRC population cells that express tgf / 32. Orange / darker grey dots represent cells that express tgf / 32. Light grey dots represent cells that do not express tgf / 32.

[0011] FIG. 5A and 5B: Show TGF[32 is secreted by SRCs. FIG. 5A shows levels, or amounts, of TGF|32 secreted by human SRCs in culture medium. FIG. 5B shows that supernatant sampled from human SRCs exhibited a time-dependent increase in secreted TGF[32 (*, p<0.05 vs. 0 hr, #, p<0.05 vs. 72 hr, **, p<0.01 vs. 0 hr).

[0012] FIG. 6: Shows gene ontology mapping that revealed tgf / 32 forms an interactome with ureteric bud (ret andfgfS') and cap mesenchyme (six2, osrl , and Ihxl) markers expressed by human SRCs.

[0013] FIG. 7A-7C: Shows assembly of SRCs into tubules in culture (FIG. 7A), and that the assembled tubules stained positive for GGT1 (FIG. 7B) and SLC12A (FIG. 7C) expression.

[0014] FIG. 8: Shows detection of SRCs ICAM-1 surface expression by flow cytometry.

[0015] FIG. 9: Shows detection of SRCs MCAM surface expression by flow cytometry.

[0016] FIG. 10: Shows SRCs have low E-cadherin surface expression.DETAILED DESCRIPTION

[0017] The present disclosure relates generally to methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, a composition including the enriched heterogeneous renal cell population identified as having therapeutic potential, and methods and uses of the enriched heterogeneous renal cell population having therapeutic potential.

[0018] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, the therapeutic potential of the enriched heterogeneous renal cell population may be in the treatment of a kidney disease, a tubular transport deficiency, or a glomerular filtration deficiency.

[0019] The therapeutic potential of the enriched heterogeneous renal cell population identified by the methods may be a restoration of kidney function, stabilization of kidney function, improvement in kidney function, reduction of renal fibrosis, reduction in renal inflammation, induction of tubulogenesis in a kidney, induction of nephrogenesis in a kidney or induction of glomerulogenesis in a kidney of a patient in need of such treatment. The therapeutic potential of the heterogeneous renal cell population identified by the methodsmay be a restoration of mineral balance, electrolyte balance, fluid homeostasis, reabsorption of essential nutrients, cystatin C metabolism, or an alleviation of anemia in a patient in need of such treatment. The therapeutic potential of the enriched heterogeneous renal cell population identified by the methods may be the potential to delay or prevent the need for dialysis, or delay or prevent the need for a kidney transplant in a patient in need of a treatment for a kidney disease.

[0020] In some methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, it may be determined whether cells of the enriched heterogeneous renal cell population express at least one cell adhesion marker. The at least one cell adhesion marker may be, or include, any one or more of intercellular adhesion molecule 5 (ICAM5), melanoma cell adhesion molecule (MCAM), contactin associated protein 1 (CNTNAP1), or matrix metallopeptidase 2 (MMP2). The at least one cell adhesion marker may be, or may include, any one, any two, any three, or all four of ICAM5, MCAM, CNTNAP1 and MMP2.

[0021] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, it may be determined whether cells of the enriched heterogeneous renal cell population express at least two of cell adhesion markers ICAM5, MCAM, CNTNAP1 and MMP2. In methods in which expression of at least two of the cell adhesion markers is determined, the two cell adhesion markers may be or include (a) ICAM5 and MCAM, (b) ICAM5 and CNTNAP1, (c) ICAM5 and MMP2, (d) MCAM and CNTNAP1, (e) MCAM and MMP2, or (f) CNTNAP1 and MMP2.

[0022] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, it may be determined whether cells of the enriched heterogeneous renal cell population express at least three of cell adhesion markers ICAM5, MCAM, CNTNAP1 and MMP2. In methods in which expression of at least three of the cell adhesion markers is determined, the three cell adhesion markers may be or include (a) ICAM5, MCAM and CNTNAP1, (b) ICAM5, MCAM and MMP2, (c) ICAM5, CNTNAP1 and MMP2, or (d) MCAM, CNTNAP1 and MMP2.

[0023] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, it may be determined whether cells of the enriched heterogeneous renal cell population express cell adhesion markers ICAM5, MCAM, CNTNAP1 and MMP2.

[0024] In the methods of identifying an enriched heterogeneous renal cell population as having therapeutic potential, determining that cells of the heterogeneous enriched renal cell population express the at least one (e.g., at least one, at least two, or at least three, or four) cell adhesion marker(s), may identify the enriched heterogeneous renal cell population as having therapeutic potential.

[0025] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, the determining expression of the at least one (at least one, or at least two, or at least three, or four) cell adhesion marker(s) may further include determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or four) cell adhesion marker(s). If the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or four) cell adhesion marker(s) is determined, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if about a certain, or particular, percentage of cells of the enriched heterogeneous renal cell population express the at least one (at least one, or at least two, or at least three, or four) cell adhesion marker(s).

[0026] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express ICAM5 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 0% and at most about 5%, greater than 0% and at most about 4.5%, greater than 0% and at most about 4%, greater than 0% and at most about 3.5%, greater than 0% and at most about 3%, greater than 0% and at most about 2.5%, greater than 0% and at most about 2%, greater than 0% and at most about 1.8%, greater than 0% and at most about 1.6%, greater than 0% and at most about 1.4%, greater than 0% and at most about 1.2%, greater than 0% and at most about 1.0%, greater than 0% and at most about 0.8%, greater than 0% and at most about 0.6%, greater than 0% and at most about 0.5%, greater than 0% and at most about 0.4%, greater than 0% and at most about 0.2%, or greater than 0% and at most about 0.1% of cells of the enriched heterogeneous renal population are determined to express ICAM5.

[0027] The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.If the degree of approximation is not otherwise clear from the context, “about” means either within plus or minus 10% of the provided value, or rounded to the nearest significant figure, in all cases inclusive of the provided value. In some embodiments, the term “about” indicates the designated value ± up to 10%, up to ± 5%, or up to ± 1%.

[0028] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express ICAM5 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 50%, e.g., greater than about 55%, greater than about 60%, greater than about 65%, greater than about 70%, greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, greater than about 95%, greater than about 96%, greater than about 97%, greater than about 98%, or greater than about 99% of cells of the enriched heterogeneous renal population are determined to express ICAM5.

[0029] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express MCAM is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 10% and at most about 35%, greater than about 10% and at most about 32.5%, greater than about 10% and at most about 30%, greater than about 10% and at most about 27.5%, greater than about 10% and at most about 25%, greater than about 12.5% and at most about 35%, greater than about 12.5% and at most about 32.5%, greater than about 12.5% and at most about 30%, greater than about 12.5% and at most about 27.5%, greater than about 12.5% and at most about 25%, greater than about 15% and at most about 35%, greater than about 15% and at most about 32.5%, greater than about 15% and at most about 30%, greater than 15% and at most about 27.5%, greater than about 15% and at most about 25%, greater than about 17.5% and at most about 35%, greater than about 17.5% and at most about 32.5%, greater than about 17.5% and at most about 30%, greater than about 17.5% and at most about 27.5%, or greater than about 17.5% and at most about 25% of cells of the enriched heterogeneous renal population are determined to express MCAM.

[0030] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express MCAM is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 50%, e.g., greater than about 55%, greater than about 60%, greater than about 65%, greater than about 70%, greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, greater than about 95%, greater than about 96%, greater than about 97%, greaterthan about 98%, or greater than about 99% of cells of the enriched heterogeneous renal cell population express MCAM.

[0031] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express CNTNAP1 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 2% and at most about 20%, if greater than about 2% and at most about 17.5%, if greater than about 2% and at most about 15%, if greater than about 2% and at most about 12.5%, if greater than about 2% and at most about 10%, greater than about 4% and at most about 20%, greater than about 4% and at most about 17.5%, greater than about 4% and at most about 15%, greater than about 4% and at most about 12.5%, greater than about 4% and at most about 10%, greater than about 6% and at most about 20%, greater than about 6% and at most about 17.5%, greater than about 6% and at most about 15%, greater than about 6% and at most about 12.5% or greater than about 6% and at most about 10% of cells of the enriched heterogeneous renal population are determined to express CNTNAP1.

[0032] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express CNTNAP1 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 10% and at most about 40%, if greater than about 10% and at most about 37.5%, if greater than about 10% and at most about 35%, if greater than about 10% and at most about 32.5%, if greater than about 10% and at most about 30%, greater than about 12.5% and at most about 40%, greater than about 12.5% and at most about 37.5%, greater than about 12.5% and at most about 35%, greater than about 12.5% and at most about 32.5%, greater than about 15% and at most about 40%, greater than about 15% and at most about 34.5%, greater than about 15% and at most about 35%, greater than about 15% and at most about 32.5% of cells of the enriched heterogeneous renal population are determined to express CNTNAP1.

[0033] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express MMP2 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 5% and at most about 30%, greater than about 5% and at most about 27.5%, greater than about 5% and at most about 25%, greater than about 5% and at most about 22.5%, greater than about 5% and at most about 20%, greater than about 7.5% and at most about 30%, greater than about 7.5% and at most about 27.5%, greater than about 7.5% and at most about 25%, greater than about 7.5% and at most about 22.5%, greater than about 7.5% and at most about 20%, greaterthan about 10% and at most about 30%, greater than about 10% and at most about 27.5%, greater than about 10% and at most about 25%, greater than about 10% and at most about 22.5%, greater than about 10% and at most about 20% of cells of the enriched heterogeneous renal cell population are determined to express MMP2.

[0034] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express MMP2 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 8% and at most about 40%, greater than about 8% and at most about 37.5%, greater than about 8% and at most about 35%, greater than about 8% and at most about 32.5%, greater than about 8% and at most about 30%, greater than about 10% and at most about 40%, greater than about 10% and at most about 37.5%, greater than about 10% and at most about 35%, greater than about 10% and at most about 32.5%, greater than about 10% and at most about 30%, greater than about 12% and at most about 40%, greater than about 12% and at most about 37.5%, greater than about 12% and at most about 35%, greater than about 12% and at most about 32.5%, greater than about 10% and at most about 30% of cells of the enriched heterogeneous renal cell population are determined to express MMP2.

[0035] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express MMP2 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 13% and at most about 40%, greater than about 13% and at most about 37.5%, greater than about 13% and at most about 35%, greater than about 13% and at most about 32.5%, greater than about 13% and at most about 30%, greater than about 15% and at most about 40%, greater than about 15% and at most about 37.5%, greater than about 15% and at most about 35%, greater than about 15% and at most about 32.5%, greater than about 15% and at most about 30%, greater than about 17% and at most about 40%, greater than about 17% and at most about 37.5%, greater than about 17% and at most about 35%, greater than about 17% and at most about 32.5%, greater than about 17% and at most about 30% of cells of the enriched heterogeneous renal cell population are determined to express MMP2.

[0036] In the methods, if the percentage of cells of the heterogeneous renal cell population that express the at least one (e.g., at least one, or at least two, or at least three, or all four) of ICAM5, MCAM, CNTNAP and MMP2 cell adhesion marker(s) is determined, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if a combination of any two, any three, or all four of the following are determined: (i) greaterthan greater than 0% and at most about 2% of cells of the heterogeneous renal cell population express ICAM5, (ii) greater than about 10% and at most about 35% of cells of the heterogeneous renal cell population express MCAM, (iii) greater than about 2% and at most about 20% of cells of the heterogeneous renal cell population express CNTNAP1, and / or (iv) greater than about 5% and at most about 30% of cells of the heterogeneous renal cell population express MMP2.

[0037] In another example, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if a combination of any two, any three, or all four of the following are determined: (i) greater than 0% and at most about 0.5% of cells of the heterogeneous renal cell population express ICAM5, (ii) greater than about 15% and at most about 30% of cells of the heterogeneous renal cell population express MCAM, (iii) greater than about 4% and at most about 15% of cells of the heterogeneous renal cell population express CNTNAP1, and / or (iv) greater than about 7.5% and at most about 25% of cells of the heterogeneous renal cell population express MMP2. In yet another example, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if a combination of any two, any three, all four of the following are determined: (i) greater than 0% and at most about 0.4% of cells of the heterogeneous renal cell population express ICAM5, (ii) greater than about 17.5% and at most about 27.5% of cells of the heterogeneous renal cell population express MCAM, (iii) greater than about 4% and at most about 12.5% of cells of the heterogeneous renal cell population express CNTNAP1, and / or (iv) greater than about 10% and at most about 20% of cells of the heterogeneous renal cell population express MMP2.

[0038] In yet another example, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if any one, any two, any three, any four, any five, or all six of the following are determined: (a) greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, (b) greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, (c) greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2, (d) greater than about 65% of cells of the enriched heterogeneous renal cell population expressMCAM and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, (e) greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2, and / or (f) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1 and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

[0039] In yet another example, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if any one, any two, any three, or all four of the following are determined: (a) (i) greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM, and (iii) greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1; (b) (i) greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM, and (iii) greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2; (c) (i) greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and (iii) greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2; and / or (d) (i) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM; (ii) greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP; and (iii) greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2.

[0040] In yet another example, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if any one, any two, any three, or all four of the following are determined: (a) (i) greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, and (iii) greater than about15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1; (b) (i) greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, and (iii) greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2; (c) (i) greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and (iii) greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2; and / or (d) (i) greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, (ii) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, (iii) greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

[0041] In another example, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if (i) greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM, (iii) greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and (iv) greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2.

[0042] In another example, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if (i) greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, (ii) greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, (iii) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and (iv) greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

[0043] The combination of any two, any three, or all four markers whose expression may be determined at these percentages may be a combination of any of (a) ICAM5 and MCAM; (b) ICAM5 and CNTNAP1; (c) ICAM5 and MMP2; (d) MCAM and CNTNAP1; (e) MCAM and MMP2; (f) CNTNAP1 and MMP2; (g) ICAM5, MCAM and CNTNAP1; (h) ICAM5,MCAM and MMP2; (i) ICAM5, CNTNAP1 and MMP2; (j) MCAM, CNTNAP1 and MMP2; or (k) ICAM5, MCAM, CNTNAP1 and MMP2.

[0044] In the method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, in addition to determining whether cells of the enriched heterogeneous renal cell population express the at least one cell adhesion marker, (e.g., any of ICAM5; or MCAM; or CNTNAP1; or MMP2; or ICAM5 and MCAM; or ICAM5 and CNTNAP1; or ICAM5 and MMP2; or MCAM and CNTNAP1; or MCAM and MMP2; or CNTNAP1 and MMP2; or ICAM5, MCAM and CNTNAP1; or ICAM5, MCAM and MMP2; or ICAM5, CNTNAP1 and MMP2; or MCAM, CNTNAP1 and MMP2; or ICAM5, MCAM, CNTNAP1 and MMP2) it may further be determined whether cells of the enriched heterogeneous renal cell population express at least one nephrogenic marker, where the at least one nephrogenic marker is one or more of homeobox protein sine oculis homeobox homolog 2 (SIX2), rearranged during transfection (RET), odd-skipped related 1 (OSR1), lim homeobox protein 1 (LHX1), or fibroblast growth factor 8 (FGF8). Determining that the cells of the enriched heterogeneous further express the at least one nephrogenic marker may identify the enriched heterogeneous renal cell population has a therapeutic potential.

[0045] The at least one nephrogenic marker whose expression may further be determined in the method may be any one of SIX2, RET, OSR1, EHX1 or FGF8. The least one nephrogenic marker whose expression may further be determined in the method may be, or may include, any of the following two nephrogenic markers: (a) SIX2 and OSR1; (b) SIX2 and EHX1; (c) SIX2 and RET; (d) SIX2 and FGF8; (e) OSR1 and LHX1; (f) OSR1 and RET; (g) OSR1 and FGF8; (h) LHX1 and RET; (i) LHX1 and FGF8; (j) RET and FGF8. The least one nephrogenic marker whose expression may be further determined in the method may be, or may include, any of the following three nephrogenic markers: (a) SIX2, OSR1 and LHX1, (b) SIX2, OSR1 and RET, (c) SIX2, OSR1 and FGF8, (d) SIX2, LHX1 and RET, (e) SIX2, LHX1 and FGF8, (f) SIX2, RET and FGF8, (g) OSR1, LHX1 and RET, (h) OSR1, LHX1 and FGF8, (i) OSR1, RET and FGF8, or (j) LHX1, RET and FGF8. The least one nephrogenic marker whose expression may be further determined in the method may be, or may include, any of the following four nephrogenic markers: (a) SIX2, OSR1, LHX1 and RET, (b) SIX2, OSR1, LHX1 and FGF8, (c) SIX2, LHX1, RET and FGF8, (d) SIX2, OSR1, RET and FGF8 or (e) OSR1, LHX1, RET and FGF8. The at least one nephrogenic marker whose expression may further be determined in the method may include five nephrogenic markers: SIX2, OSR1, LHX1, RET and FGF8.

[0046] In the method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, where the expression of the at least one nephrogenic marker (in addition to the at least one, at least two, at least three or four cell adhesion markers) is further determined, the determined expression of the at least one (at least one, or at least two, or at least three, or at least four, or all five) nephrogenic marker(s) may further include determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s). If the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if about a certain, or particular, percentage of cells of the enriched heterogeneous renal cell population are determined express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s).

[0047] In instances of the methods in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, if the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is, or includes SIX2, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if greater than 0% and at most about 10%, or greater than about 0% and at most about 8%, or greater than 0% and at most about 6%, or greater than 0% and at most about 5.5%, or greater than 0% and at most about 5%, or greater than 0% and at most about 4.5%, or greater than 0% and at most about 4%, or greater than 0% and at most about 3.5%, or greater than 0% and at most about 3%, or greater than 0% or at most about 2.5%, or greater than 0% and at most about 2%, or greater than 0% and at most about 1.5%, or greater than 0% and at most about 1%, or greater than 0% and at most about 0.8%, or greater than 0% and at most about 0.6%, or greater than 0% and at most about 0.4%, or greater than 0% and at most about 0.2% of cells of the enriched heterogeneous renal cell population are further determined to express SIX2.

[0048] In instances of the methods in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, if the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenicmarker(s) is, or includes OSR1, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if greater than 0% and at most about 90%, greater than 0% and at most about 85%, greater than 0% and at most about 80%, greater than 0% and at most about 75%, greater than 0% and at most about 70%, greater than 0% and at most about 65%, greater than 0% and at most about 60%, greater than 0% and at most about 55%, greater than 0% and at most about 50%, greater than 0% and at most about 45%, greater than 0% and at most about 40%, greater than 0% and at most about 35%, greater than 0% and at most about 30%, greater than 0% and at most about 25%, greater than 0% and at most about 20%, greater than 0% and at most about 15%, greater than 0% and at most about 10%, greater than about 0.15% and at most about 8%, greater than about 0.15% and at most about 9%, greater than about 0.15% and at most about 10%, greater than about 0.15% and at most about 11%, greater than about 0.15% and at most about 12%, greater than about 35% and at most about 90%, greater than about 35% and at most about 85%, greater than about 35% and at most about 80%, greater than about 35% and at most about 75%, greater than about 35% and at most about 70%, greater than about 40% and at most about 90%, greater than about 45% and at most about 90%, greater than about 50% and at most about 90%, greater than about 55% and at most about 90%, greater than about 60% and at most about 90%, or greater than about 65% and at most about 90% of cells of the enriched heterogeneous renal cell population are further determined to express OSR1.

[0049] In instances of the methods in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, if the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is, or includes LHX1, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if greater than about 5% and at most about 90%, greater than about 5% and at most about 85%, greater than about 5% and at most about 80%, greater than about 5% and at most about 75%, greater than about 5% and at most about 70%, greater than about 5% and at most about 65%, greater than about 5% and at most about 60%, greater than about 5% and at most about 55%, greater than about 5% and at most about 50%, greater than about 5% and at most about 45%, greater than about 5% and at most about 40%, greater than about 10% and at most about 90%, greater than about 10% and at most about 85%, greater than about 10% and at most about 80%, greater than about 10% and at most about 75%, greater than about 10% and at most about 70%, greater than about 10% and atmost about 65%, greater than about 10% and at most about 60%, greater than about 10% and at most about 55%, greater than about 10% and at most about 50%, greater than about 10% and at most about 45%, greater than about 10% and at most about 40%, greater than about 15% and at most about 90%, greater than about 15% and at most about 85%, greater than about 15% and at most about 80%, greater than about 15% and at most about 75%, greater than about 15% and at most about 70%, greater than about 15% and at most about 65%, greater than about 15% and at most about 60%, greater than about 15% and at most about 55%, greater than about 15% and at most about 50%, greater than about 15% and at most about 45%, greater than about 15% and at most about 40%, greater than about 20% and at most about 90%, greater than about 20% and at most about 85%, greater than about 20% and at most about 80%, greater than about 20% and at most about 75%, greater than about 20% and at most about 70%, greater than about 20% and at most about 65%, greater than about 20% and at most about 60%, greater than about 20% and at most about 55%, greater than about 20% and at most about 50%, greater than about 20 and at most about 45%, or greater than about 20% and at most about 40% of cells of the enriched heterogeneous renal cell population are further determined to express LHX1.

[0050] In instances of the methods in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, if the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is, or includes RET, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if greater than 0% and at most about 90%, greater than 0% and at most about 80%, greater than 0% and at most about 70%, greater than 0% and at most about 60%, greater than 0% and at most about 50%, greater than 0% and at most about 45%, greater than 0% and at most about 40%, greater than 0% and at most about 35%, greater than 0% and at most about 30%, greater than 0% and at most about 25%, greater than 0% and at most about 20%, greater than 0% and at most about 15%, greater than 0% and at most about 10%, greater than 0% and at most about 9%, greater than 0% and at most about 8%, greater than 0% and at most about 7%, greater than 0% and at most about 6%, greater than 0% and at most about 5%, greater than 0% and at most about 4%, greater than 0% and at most about 3%, greater than 0% and at most about 2%, greater than 0% and at most about 1%, greater than about 0.2% and at most about 10%, greater than about 0.2% and at most about 9%, greater than about 0.2% and at most about 8%, greater than about 0.2% and atmost about 7%, greater than about 0.2% and at most about 6%, greater than about 0.2% and at most about 5%, greater than about 0.2% and at most about 4%, greater than about 0.2% and at most about 3%, greater than about 0.2% and at most about 2%, or greater than about 0.2% and at most about 1% of cells of the enriched heterogeneous renal cell population are further determined to express RET.

[0051] In instances of the methods in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, if the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is, or includes FGF8, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if greater than 0% and at most about 60%, greater than 0% and at most about 50%, greater than 0% and at most about 40%, greater than 0% and at most about 30%, greater than 0% and at most about 20%, greater than 0% and at most about 10%, greater than 0% and at most about 9%, greater than 0% and at most about 8%, greater than 0% and at most about 7%, greater than 0% and at most about 6%, greater than 0% and at most about 5%, greater than 0% and at most about 4%, greater than 0% and at most about 3%, greater than 0% and at most about 2%, greater than 0% and at most about 1%, greater than 0% and at most about 0.9%, greater than 0% and at most about 0.8%, greater than 0% and at most about 0.7%, greater than 0% and at most about 0.6%, greater than 0% and at most about 0.5%, greater than 0% and at most about 0.4%, greater than 0% and at most about 0.3%, greater than 0% and at most about 0.2%, or greater than 0% and at most about 0.1% of cells of the enriched heterogeneous renal cell population are further determined to express FGF8.

[0052] By way of example, in instances of the methods in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if a combination of any two, any three, any four or all of the following are further determined: (i) greater than 0% and at most about 0.2% of cells of the enriched heterogeneous renal cell population express SIX2, (ii) greater than about .015 and at most about 11% of cells of the enriched heterogeneous renal cell population express OSR1, (iii) greater than about 20% and at most about 40% of cells of the enriched heterogeneous renal cell population express EHX1, (iv) greater than about 0.2% and at most about 0.6% of cellsof the enriched heterogeneous renal cell population express RET and / or (v) greater than 0% and at most about 0.3% of cells of the enriched heterogeneous renal cell population express FGF8. In another example of an instance of the method in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if a combination of any two, any three, any four or all five of the following are further determined: (i) greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, (ii) greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, (iii) greater than about 8% and at most about 90% of cells of the enriched heterogeneous renal cell population express EHX1, (iv) greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and / or (v) greater than 0% and at most about 60% of cells of the enriched heterogeneous renal cell population express FGF8. In another example of an instance of the method in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if a combination of any two, any three, any four or all five of the following are further determined: (i) greater than about 0.1% and at most about 10% of cells of the enriched heterogeneous renal cell population express SIX2, (ii) greater than about 0.15% and at most about 80% of cells of the enriched heterogeneous renal cell population express OSR1, (iii) greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express EHX1, (iv) greater than 10% and at most about 80% of cells of the enriched heterogeneous renal cell population express RET and / or (v) greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express FGF8. The combination of any two, any three, any four, or all five markers whose expression may further be determined at these percentages may be a combination of any of SIX2 and OSR1; SIX2 and LHX1; SIX2 and RET; SIX2 and FGF8; OSR1 and LHX1; OSR1 and RET; OSR1 and FGF8; LHX1 and RET; LHX1 and FGF8; RET and FGF8; SIX2, OSR1 and LHX1; SIX2, OSR1 and RET; SIX2, OSR1 and FGF8; SIX2, LHX1 and RET; SIX2, LHX1 and FGF8; SIX2, RET and FGF8; OSR1, LHX1 and RET; OSR1, LHX1 and FGF8; OSR1, RET and FGF8; LHX1, RET and FGF8; SIX2, OSR1,LHX1 and RET; SIX2, 0SR1, LHX1 and FGF8; SIX2, EHX1, RET and FGF8; SIX2, OSR1, RET and FGF8; OSR1, LHX1, RET and FGF8; or SIX2, OSR1, LHX1, RET and FGF8.

[0053] In the methods of determining an enriched heterogeneous renal cell population has a therapeutic potential, the determining the expression of the at least one cell adhesion marker (the at least one, at least two, at least three or four of ICAM5, MCAM, CNTNAP1 or MMP2), may further determine expression of at least one additional cell adhesion marker, where the at least one additional cell adhesion marker may include any one or more of collagen type XI alpha 1 (COL11A1), platelet endothelial cell adhesion molecule (PECAM)l, and / or E-cadherin. The determining the expression of the at least one cell adhesion marker and the at least one additional cell adhesion marker may identify the enriched heterogeneous renal cell population as having therapeutic potential.

[0054] In some instances, the determining the expression of the at least one additional cell adhesion molecule, (additional to the at least one, at least two, at least three or four of ICAM5, MCAM, CNTNAP1 and / or MMP2) may be a determining of the percentage of cells of the enriched heterogeneous renal cell population that express the at least one additional cell adhesion marker. In instances in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one additional cell adhesion marker is determined, and the additional cell adhesion molecule may be, or include, COL11A1. In these instances, the percent cells that express COL11A1 that may further be determined to identify the enriched heterogeneous renal cell population as having a therapeutic potential may be greater than about 15% and at most about 40%, greater than about 16% and at most about 40%, greater than about 17% and at most about 40%, greater than about 18% and at most about 40%, greater than about 19% and at most about 40%, greater than about 20% and at most about 40%, greater than about 20% and at most about 41%, greater than about 20% and at most about 42%, greater than about 20% and at most about 43%, greater than about 20% and at most about 44%, greater than about 20% and at most about 45%, greater than 20% and at most about 46%, greater than 20% and at most about 48%, greater than 20% and at most about 50%, greater than 20% and at most about 52%, greater than 20% and at most about 54%, greater than 20% and at most about 55%, greater than about 25% and at most about 40%, greater than about 25% and at most about 42%, greater than 25% and at most about 44%, greater than about 25% and at most about 46%, greater than about 25% and at most about 48%, greater than about 25% and at most about 50%, greater than about 25% and at most about 52%, greater than about 25% and atmost about 54%, greater than about 25% and at most about 55%, greater than about 15% and at most about 41%, greater than about 15% and at most about 42%, greater than about 15% and at most about 43%, greater than about 15% and at most about 44%, greater than about 15% and at most about 45%.

[0055] In instances in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one additional cell adhesion marker is determined, and the additional cell adhesion molecule is, or includes, PECAM1, the percent cells that express PEC AMI that may further be determined to identify the enriched heterogeneous renal cell population as having a therapeutic potential may be a percentage greater than 0% and at most about 5%, greater than 0% and at most about 4%, greater than 0% and at most about 3%, greater than 0% and at most about 2%, greater than 0% and at most about 1%, greater than 0% and at most about 0.5%, greater than 0% and at most about 0.4%, greater than 0% and at most about 0.3%.

[0056] In instances in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one additional cell adhesion marker is determined, and the additional cell adhesion molecule is, or includes, CDH1 (a.k.a. E-cadherin), the percent cells that express CDH1 that may further be determined to identify the enriched heterogeneous renal cell population as having a therapeutic potential may be greater than about 8% and at most about 40%, greater than about 8% and at most about 39%, greater than about 8% and at most about 38%, greater than about 8% and at most about 37%, greater than about 8% and at most about 36%, greater than about 8% and at most about 35%, greater than about 10% and at most about 20%, greater than about 10% and at most about 19%, greater than about 10% and at most about 18%, greater than about 10% and at most about 17%, greater than about 10% and at most about 40%, greater than about 11% and at most about 40%, greater than about 12% and at most about 40%, greater than about 13% and at most about 40%, greater than about 14% and at most about 40%, greater than about 15% and at most about 40%, greater than about 16% and at most about 40%, greater than about 17% and at most about 40%, greater than about 18% and at most about 40%, greater than about 19% and at most about 40%, greater than about 15% and at most about 39%, greater than about 15% and at most about 38%, greater than about 15% and at most about 37%, greater than about 15% and at most about 36%, greater than about 15% and at most about 35%, greater than about 15% and at most about 34% or greater than about 15% and at most about 33%. In such instances, the percent cells that express CDH1 may be percent cells that express CDH1 mRNA. In otherinstances, the percent cells that express CDH1 may be greater than 0% and at most about 5, or greater than 0% and at most about 4.5%, or greater than about 0% and at most about 4%, greater than 0% and at most about 3.5%, greater than about 0% and at most about 3.0%, greater than 0% and at most about 2.5%, greater than about 0% and at most about 2%, greater than 0% and at most about 1.5%, greater than 0% and at most about 1% or greater than 0% and at most about 0.5%. In these instances, the percent cells that express CDH1 may be percent cells that express CDH1 protein on their surface.

[0057] In the methods of determining an enriched heterogeneous renal cell population has a therapeutic potential, the determining may not only include determining the expression of the at least one cell adhesion marker (the at least one, at least two, at least three or four of any of ICAM5, MCAM, CNTNAP1 and / or MMP2) and, optionally, the expression of the at least one nephrogenic marker (the at least one, at least two, at least three, at least four, or five of any of SIX1, RET, OSR1, LHX1 and / or FGF8) and, optionally, the expression of the at least one additional cell adhesion marker (any one, or two or three of COE11A1, PEC AMI and / or E-cadherin), it may further, optionally, include determining expression of one or more further markers. Examples of further markers include, but are not limited to TGF|32, nephrin, podocin, or receptor for activated C kinase (RACK-1). The further determination of expression of the at least one further marker may identify the enriched heterogeneous renal cell population as having a therapeutic potential. In some instances, the further determining that cells of the enriched heterogeneous renal cell population express the at least one further marker may be a determining that a certain percentage of cells of the enriched heterogeneous renal cell population express the at least one further marker.

[0058] In instances of the method in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one further marker is further determined, and the further marker is, or includes, TGF|32, the percent cells that express TGF|32 that may identify the enriched heterogeneous renal cell population as having a therapeutic potential may be greater than about 40% and at most about 85%, greater than about 40% and at most about 80%, greater than about 40% and at most about 75%, greater than about 40% and at most about 70%, greater than about 45% and at most about 85%, greater than about 45% and at most about 80%, greater than about 45% and at most about 75%, greater than about 45% and at most about 70%, greater than about 50% and at most about 85%, greater than about 50% and at most about 80%, greater than about 50% and at most about 75%, greater than about 50% and at most about 70%, greater than about 55% andat most about 85%, greater than about 50% and at most about 80%, greater than about 50% and at most about 75% or greater than about 50% and at most about 80%.

[0059] In instances of the method in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one further marker is further determined, and the further marker is, or includes, nephrin, the percent cells that express nephrin that may identify the enriched heterogeneous renal cell population as having a therapeutic potential may be greater than about 68%, greater than about 70%, greater than about 72%, greater than about 74%, greater than about 76%, greater than about 78%, greater than about 80%, greater than about 82%, greater than about 84%, greater than about 86%, greater than about 88%, greater than about 90%, greater than about 92%, greater than about 94%, greater than about 96%, greater than about 98%, or about 100% or greater than about 65% and at most about 99%, or greater than about 70% and at most about 99%, or greater than about 75% and at most about 99%, or greater than about 80% and at most about 99%, or greater than about 85% and at most about 99%.

[0060] In instances of the method in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one further marker is further determined, and the further marker is, or includes, podocin, the percent cells that express podocin that may identify the enriched heterogeneous renal cell population as having a therapeutic potential may be greater than about 91%, greater than about 92%, greater than about 93%, greater than about 94%, greater than about 95%, greater than about 96%, greater than about 97%, greater than about 98%, greater than about 98%, or about 100%.

[0061] In instances of the method in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one further marker is further determined, and the further marker is, or includes, RACK1, the percent cells that express RACK1 that may identify the enriched heterogeneous renal cell population as having a therapeutic potential may be greater than about 80%, greater than about 81%, greater than about 82%, greater than about 83%, greater than about 84%, greater than about 85%, greater than about 86%, greater than about 87%, greater than about 88%, greater than about 89%, greater than about 90%, greater than about 91%, greater than about 92%, greater than about 93%, greater than about 94%, greater than about 95%, greater than about 96%, greater than about 97%, greater than about 98%, greater than about 99% or about 100%.

[0062] In the methods of determining an enriched heterogeneous renal cell population has a therapeutic potential, the determining may not only include determining the expression of the at least one cell adhesion marker (the at least one, at least two, at least three or four of any of ICAM5, MCAM, CNTNAP1 and / or MMP2) and, optionally, the expression of the at least one nephrogenic marker (the at least one, at least two, at least three, at least four, or five of any of SIX1, RET, OSR1, LHX1 and / or FGF8) and, optionally, the expression of the at least one additional cell adhesion marker (any one, or any two or three of COE11A1, PEC AMI and / or E-cadherin) and, optionally, the expression of one or more further markers (e.g., TGF|32, nephrin, podocin, and / or RACK-1), it may further, optionally, determine whether cells of the enriched heterogeneous renal cell population secrete TGF|32. In some instances, if cells of the enriched heterogeneous renal cell population are further determined to secrete TGF|32, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential. In some instances, the determining cells of the enriched heterogeneous renal cell population secrete TGF|32 may be a determining that cells of the enriched heterogeneous renal cell population secrete a certain amount of about TGF|32. In such instances, it may be further determined that greater than about 1 ng TGF|32 per million cells, greater than about 1.2 ng TGF|32 per million cells, greater than about 1.4 ng TGF|32 per million cells, greater than about 1.6 ng TGF|32 per million cells, greater than about 1.8 ng TGF|32 per million cells, greater than about 2.0 ng TGF|32 per million cells, greater than about 2.2 ng TGF|32 per million cells, greater than about 2.4 ng TGF|32 per million cells, greater than about 2.6 ng TGF|32 per million cells, greater than about 2.8 ng TGF|32 per million cells, greater than about 3.0 ng TGF|32 per million cells, greater than about 3.5 ng TGF|32 per million cells, greater than about 4.0 ng TGF|32 per million cells, greater than about 4.5 ng TGF|32 per million cells, greater than about 5.0 ng TGF|32 per million cells, greater than about 5.5 ng TGF|32 per million cells, greater than about 6.0 ng TGF|32 per million cells, greater than about 6.5 ng TGF|32 per million cells, greater than about 7.0 ng TGF|32 per million cells, greater than about 7.5 ng TGF|32 per million cells, greater than about 8.0 ng TGF|32 per million cells, greater than about 8.5 ng TGF|32 per million cells, greater than about 9.0 ng TGF|32 per million cells, greater than about 9.5 ng TGF|32 per million cells, greater than about 10.0 ng TGF|32 per million cells, greater than about 11.0 ng TGF|32 per million cells, greater than about 12.0 ng TGF|32 per million cells, greater than about 13.0 ng TGF|32 per million cells, greater than about 14.0 ng TGF|32 per million cells,greater than about 15.0 ng TGF|32 per million cells, or about 1 ng to about 40 ng TGF|32 per million cells, about 1 ng to about 35 ng TGF|32 per million cells, about 1 ng to about 30 ng TGF|32 per million cells, about 1 ng to about 25 ng TGF|32 per million cells, about 1 ng to about 20 ng TGF|32 per million cells, about 2 ng to about 40 ng TGF|32 per million cells, about 2 ng to about 35 ng TGF|32 per million cells, about 2 ng to about 30 ng TGF|32 per million cells, about 2 ng to about 25 ng TGF|32 per million cells, about 2 ng to about 20 ng TGF|32 per million cells, about 3 ng to about 40 ng TGF|32 per million cells, about 3 ng to about 35 ng TGF|32 per million cells, about 3 ng to about 30 ng TGF|32 per million cells, about 3 ng to about 25 ng TGF|32 per million cells, or about 3 ng to about 20 ng TGF|32 per million cells is secreted to identify the enriched heterogeneous renal cell population as having a therapeutic potential. The cells may secrete the amount TGF|32 per million cells, e.g., in culture media after being in culture, in about 24 hours, about 30 hours, about 36 hours, about 42 hours, about 48 hours, about 54 hours, about 60 hours, about 66 hours, about 72 hours, about 78 hours, about 84 hours, about 90 hours, about 96 hours, about 102 hours, or about 108 hours.

[0063] By way of example, in some instances of the methods, if cells of the enriched heterogeneous renal cell population are further determined to secrete TGF|32, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is further determined that greater than about .7 ng, greater than about .8 ng, greater than about .9 ng, greater than 1.0 ng, greater than about 1.1 ng, greater than about 1.2 ng, between about .7 ng and about 1.75 ng, between about .7 ng and about 1.5 ng, between about .7 ng and about 1.25 ng, between about .8 ng and about 1.75 ng, between about .8 ng and about 1.5 ng, between about .8 ng and about 1.25 ng, between about .9 ng and about 1.75 ng, between about .9 ng and about 1.5 ng, between about .9 ng and about 1.25 ng, between about 1.0 ng about 1.75 ng, or between about 1.0 ng and about 1.5 ng TGF|32 is secreted per million cells over (or within) a time period of about 18 hours, about 24 hours, about 30 hours, about 36 hours, about 20 hours to about 36 hours, about 18 hours to about 30 hours, about 18 to 24 hours, about 24 hours to about 36 hours, or about 24 hours to about 30 hours.

[0064] By way of other example, if cells of the enriched heterogeneous renal cell population are further determined to secrete TGF|32, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is further determined that greater than about 3.5 ng, greater than about 3.7 ng, greater than about 3.9 ng. greater than 4.1 ng, greaterthan about 4.3 ng, greater than about 4.5 ng, or between about 3.5 ng and about 8.0 ng, between about 3.5 ng and about 7.5 ng, between about 3.5 ng and about 7.0 ng, between about 3.9 ng and about 8.0 ng, between about 3.9 ng and about 7.5 ng, between about 3.9 ng and about 7.0 ng, between about 4.1 ng and about 8.0 ng, between about 4.1 ng and about 7.5 ng, between about 4.1 ng and about 7.0 ng, between about 4.5 ng about 8.0 ng, between about 4.5 ng and about 7.5 ng or between 4.5 ng and about 7.0 ng TGF|32 is secreted per million cells over (or within) a time period of about 36 hours, about 42 hours, about 48 hours, about 54 hours, about 60 hours, about 36 hours to about 60 hours, about 36 hours to about 54 hours, about 36 hours and to about 48 hours, about 42 hours to about 60 hours, about 42 hours to about 54 hours, or about 42 hours to about 48 hours.

[0065] In yet a further example, if cells of the enriched heterogeneous renal cell population are further determined to secrete TGF|32, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is further determined that greater than about 8.0 ng, greater than about 8.25 ng, greater than about 8.5 ng, greater than about 8.75 ng, greater than about 9.0 ng, between about 8.0 ng and about 25 ng, between about 8.0 ng and about 20 ng, between about 8.0 ng and about 15 ng, between about 8.25 ng and about 25 ng, between about 8.25 ng and about 20 ng, between about 8.25 ng and about 15 ng, between about 8.5 ng and about 25 ng, between about 8.5 ng and about 20 ng, between about 8.5 ng about 15 ng, between about 8.75 ng and about 25 ng or between 8.75 ng and about 20 ng or about 8.75 and about 15 ng TGF|32 is secreted per million cells over (or within) a time period of about 60 hours, about 72 hours, about 78 hours, about 84 hours, about 60 hours to about 84 hours, about 60 hours to about 78 hours, about 60 hours to about 72 hours, about 72 hours to about 84 hours, or about 72 hours to about 78 hours.

[0066] In another method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential provided by the disclosure, an enriched heterogeneous renal cell population may be identified as having a therapeutic potential by determining expression of TGF|32 by cells of the enriched heterogeneous renal cell population. In these methods, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if it is determined that (i) greater than about 50% of cells of the enriched heterogenous renal cell population express TGF[32 and / or (ii) TGF|32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 1.0 ng or about 2.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

[0067] In these other methods, methods in which expression of TGF|32 by cells of the enriched heterogeneous renal cell population is determined, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if it is determined that greater than about 50% of cells of the enriched heterogenous renal cell population express TGF[32. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 40% and at most about 85%, greater than about 40% and at most about 80%, greater than about 40% and at most about 75%, greater than about 40% and at most about 70%, greater than about 45% and at most about 85%, greater than about 45% and at most about 80%, greater than about 45% and at most about 75%, greater than about 45% and at most about 70%, greater than about 50% and at most about 85%, greater than about 50% and at most about 80%, greater than about 50% and at most about 75%, greater than about 50% and at most about 70%, greater than about 55% and at most about 85%, greater than about 55% and at most about 80% or greater than about 55% and at most about 75% of cells of the enriched heterogeneous renal cell population are determined to express TGF[32. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 40%, greater than about 42.5%, greater than about 45%, greater than about 47.5%, greater than about 50%, greater than about 52.5%, greater than about 55%, greater than about 57.5% or greater than about 60% of cells of the enriched heterogeneous renal cell population are determined to express TGF[32.

[0068] In these other methods, methods in which expression of TGF|32 by cells of the enriched heterogeneous renal cell population is determined, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if it is determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 1.0 ng per 1,000,000 enriched heterogeneous renal cell population cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount greater than about 1 ng, or greater than about 1.2 ng, or greater than about 1.4 ng, or greater than about 1.6 ng, or greater than about 1.8 ng, or greater than about 2 ng, or greater than about 2.2 ng, or greater than about 2.4 ng, or greater than about 2.6 ng, or greater than about 2.8 ng, or greater than about 3.0 ng, or greater than about 3.5 ng, or greater than about 4.0 ng, or greater than about 4.5 ng, or greater than about 5.0 ng, or greater than about 5.5 ng, or greater than about 6.0 ng, or greater than about 6.5 ng, or greater thanabout 7.0 ng, or greater than about 7.5 ng, or greater than about 8.0 ng, or greater than about8.5 ng, or greater than about 9.0 ng, or greater than about 9.5 ng, or greater than about 10 ng, or greater than about 11 ng, or greater than about 12 ng, or greater than about 13 ng, or greater than about 14 ng or greater than about 15 ng per million cells. Alternatively, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of about 1 ng to about 40 ng per million cells, or about 1 ng to about 35 ng per million cells, or about 1 ng to about 30 ng per million cells, or about 1 ng to about 25 ng per million cells, or about 1 ng to about 20 ng per million cells, about 2 ng to about 40 ng per million cells, or about 2 ng to about 35 ng per million cells, or about 2 ng to about 30 ng per million cells, or about 2 ng to about 25 ng per million cells, or about 2 ng to about 20 ng per million cells, or about 3 ng to about 40 ng per million cells, or about 3 ng to about 35 ng per million cells, or about 3 ng to about 30 ng per million cells, or about 3 ng to about 25 ng per million cells, or about 3 ng to about 20 ng per million cells. The secreted TGF[32 by the cells of the enriched heterogeneous renal cell population in these amounts, may be, e.g., in culture media, over (or within) a time period of about 24 hours, about 30 hours, about 36 hours, about 42 hours, about 48 hours, about 54 hours, about 60 hours, about 66 hours, about 72 hours, about 78 hours, about 84 hours, about 90 hours, about 96 hours, about 102 hours, about 108 hours, or between about 24 hours to about 108 hours, or between about 36 hours to about 108 hours, or between about 24 hours and about 90 hours, or between about 24 hours and about 72 hours, or between about 48 hours and about 72 hours.

[0069] In instances of these other methods, methods in which expression of TGF|32 by cells of the enriched heterogeneous renal cell population is determined, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if cells of the enriched heterogeneous renal cell population are determined to secrete greater than about .7 ng, greater than about .8 ng, greater than about .9 ng, greater than 1.0 ng, greater than about 1.1 ng, greater than about 1.2 ng, greater than 1.4 ng, greater than 1.5 ng, greater than 2.0 ng, greater than 2.5 ng, between about .7 ng and about 1.75 ng, between about .7 ng and about1.5 ng, between about .7 ng and about 1.25 ng, between about .8 ng and about 1.75 ng, between about .8 ng and about 1.5 ng, between about .8 ng and about 1.25 ng, between about .9 ng and about 1.75 ng, between about .9 ng and about 1.5 ng, between about .9 ng and about 1.25 ng, between about 1.0 ng about 1.75 ng, between about 1.0 ng and about 1.5 ng, between about 4.0 ng, between about 1.0 ng and about 5.0 ng, between about 1.0 ng and about 6.0 ng,between about 1.0 ng and about 7.0 ng, between about 2.0 ng and about 4.0 ng, between about 2.0 ng and about 5.0 ng, between about 2.0 ng and about 6.0 ng, or between 2.0 ng and about 7.0 ng TGF|32 per million cells over (or within) a time period of about 18 hours, about 24 hours, about 30 hours, about 36 hours, about 20 hours to about 36 hours, about 18 hours to about 30 hours, about 18 hours to about 24 hours, about 24 hours to about 36 hours or about 24 hours to about 30 hours.

[0070] In other instances of these methods, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if cells the enriched heterogeneous renal cell population are determined to secrete greater than about 3.5 ng, greater than about 3.7 ng, greater than about 3.9 ng. greater than 4.1 ng, greater than about 4.3 ng, greater than about 4.5 ng, between about 3.5 ng and about 8.0 ng, between about 3.5 ng and about 7.5 ng, between about 3.5 ng and about 7.0 ng, between about 3.9 ng and about 8.0 ng, between about 3.9 ng and about 7.5 ng, between about 3.9 ng and about 7.0 ng, between about 4.1 ng and about 8.0 ng, between about 4.1 ng and about 7.5 ng, between about 4.1 ng and about 7.0 ng, between about 4.5 ng about 8.0 ng, between about 4.5 ng and about 7.5 ng or between 4.5 ng and about 7.0 ng TGF|32 per million cells over (or within) a time period of about 36 hours, about 42 hours, about 48 hours, about 54 hours, about 60 hours, about 36 hours to about 60 hours, about 36 hours to about 54 hours, about 36 hours and to about 48 hours, about 42 hours to about 60 hours, about 42 hours to about 54 hours or about 42 hours to about 48 hours.

[0071] In yet other instances of these methods, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if cells the enriched heterogeneous renal cell population are determined to secrete greater than about 8.0 ng, greater than about 8.25 ng, greater than about 8.5 ng, greater than about 8.75 ng, greater than about 9.0 ng, between about 8.0 ng and about 25 ng, between about 8.0 ng and about 20 ng, between about 8.0 ng and about 15 ng, between about 8.25 ng and about 25 ng, between about 8.25 ng and about 20 ng, between about 8.25 ng and about 15 ng, between about 8.5 ng and about 25 ng, between about 8.5 ng and about 20 ng, between about 8.5 ng about 15 ng, between about 8.75 ng and about 25 ng, between 8.75 ng and about 20 ng or about 8.75 and about 15 ng TGF|32 per million cells over (or within) a time period of about 60 hours, about 72 hours, about 78 hours, about 84 hours, about 60 hours to about 84 hours, about 60 hours to about 78 hours, about 60 hours to about 72 hours, about 72 hours to about 84 hours or about 72 hours to about 78 hours. 1

[0072] In these other methods, methods in which expression of TGF|32 by cells of the enriched heterogeneous renal cell population is determined, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if it is determined that both: (i) about a certain percentage of cells of the population express TGF|32 and (ii) about a certain amount of TGF[32 is secreted by cells of the enriched heterogeneous renal cell population. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) greater than about 50% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF|32 is secreted in an amount of at least about 1.0 ng, 1.5 ng, 2.0 ng, 2.5 ng, 3.0 ng, 3.5 ng, 4.0 ng,4.5 ng or 5.0 ng per million cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) about 50% to about 80% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF[32 is secreted in an amount of at least about 1.0 ng, 1.5 ng, 2.0 ng, 2.5 ng, 3.0 ng, 3.5 ng, 4.0 ng, 4.5 ng or 5.0 ng per million cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) greater than about 55% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF[32 is secreted in an amount of at least about 1.0 ng,1.5 ng, 2.0 ng, 2.5 ng, 3.0 ng, 3.5 ng, 4.0 ng, 4.5 ng or 5.0 ng per million cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) about 55% to about 75% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF|32 is secreted in an amount of at least about 1.0 ng, 1.5 ng, 2.0 ng, 2.5 ng, 3.0 ng, 3.5 ng, 4.0 ng, 4.5 ng, or 5.0 ng per million cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) greater than about 50% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF|32 is secreted in an amount of at least about 1.0 ng to about 50 ng, or about 2.0 ng to about 40 ng, or about 3.0 ng to about 30 ng per million cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) about 50% to about 80% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF[32 is secreted in an amount of about 1.0 ng to about 50 ng, or about 2.0 ng to about 40 ng, or about 3.0 ng to about 30 ng per million cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) greater than about 55% of cells of theenriched heterogeneous renal cell population express TGF[32 and (ii) TGF|32 is secreted in an amount of about 1.0 ng to about 50 ng, or about 2.0 ng to about 40 ng, or about 3.0 ng to about 30 ng per million cells. In some instances, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that (i) about 55% to about 75% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF[32 is secreted in an amount of about 1.0 ng to about 50 ng, or about 2.0 ng to about 40 ng, or about 3.0 ng to about 30 ng per million cells. In these instances, the amount TGF[32 secreted by the cells may be secreted over a time period of about 24 hours to about 120 hours or about 24 hours, about 36 hours, about 24 hours to about 72 hours, about 48 hours to about 120 hours, about 48 hours to about 96 hours, about 48 hours, about 72 hours, about 96 hours or about 120 hours.

[0073] By way of example, in these other methods, methods in which expression of TGF|32 by cells of the enriched heterogeneous renal cell population is determined, the enriched heterogenous renal cell population may be identified as having a therapeutic potential if it is determined that both: (i) greater than about 50%, or greater than about 55% or between about 50% of cells of the enriched heterogeneous renal cell population express TGF[32 and (ii) TGF[32 is secreted, where TGF[32 is secreted in an amount of at least about (a) 0.7 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 24-hour time period, (b) 3.5 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 48-hour time period; and / or (c) 8.0 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 72-hour time period. In some instances of such an example, the amount TGF[32 secreted over the approximate 24-hour time period may be at least about 1.0 ng, at least about 1.5 ng, at least about 2.0 ng or at least about 2.5 ng per 1,000,000 enriched heterogeneous renal cell population cells.

[0074] In these other methods, methods in which expression of TGF|32 by cells of the enriched heterogeneous renal cell population is determined, expression of at least one nephrogenic marker may also be determined, where the at least one nephrogenic marker is one or more of SIX2, RET, OSR1, LHX1, or FGF8. Determining that the cells of the enriched heterogeneous renal cell population further express the at least one nephrogenic marker, in addition to TGF|32, may identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0075] The at least one nephrogenic marker whose expression may further be determined in the method may be any one of SIX1, RET, OSR1, LHX1 or FGF8. The least one nephrogenic marker whose expression may further be determined in the method may be, or may include, any of the following two nephrogenic markers: (a) SIX2 and OSR1; (b) SIX2 and EHX1; (c) SIX2 and RET; (d) SIX2 and FGF8; (e) OSR1 and EHX1; (f) OSR1 and RET; (g) OSR1 and FGF8; (h) LHX1 and RET; (i) LHX1 and FGF8; (j) RET and FGF8. The least one nephrogenic marker whose expression may be further determined in the method may be, or may include, any of the following three nephrogenic markers: (a) SIX2, OSR1 and LHX1, (b) SIX2, OSR1 and RET, (c) SIX2, OSR1 and FGF8, (d) SIX2, LHX1 and RET, (e) SIX2, LHX1 and FGF8, (f) SIX2, RET and FGF8, (g) OSR1, LHX1 and RET, (h) OSR1, LHX1 and FGF8, (i) OSR1, RET and FGF8, or (j) LHX1, RET and FGF8. The least one nephrogenic marker whose expression may be further determined in the method may be, or may include, any of the following four nephrogenic markers: (a) SIX2, OSR1, LHX1 and RET, (b) SIX2, OSR1, LHX1 and FGF8, (c) SIX2, LHX1, RET and FGF8, (d) SIX2, OSR1, RET and FGF8 or (e) OSR1, LHX1, RET and FGF8. The at least one nephrogenic marker whose expression may further be determined in the method may include all five nephrogenic markers: SIX2, OSR1, LHX1, RET and FGF8.

[0076] In these methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, where the expression of the at least one nephrogenic marker (in addition TGF[32 expression) is further determined, the determined expression of the at least one (at least one, or at least two, or at least three, or at least four, or all five) nephrogenic marker(s) may further include determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s). If the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (at least one, at least two, or at least three, or at least four, or five) nephrogenic marker(s) is further determined, then the enriched heterogeneous renal cell population may be identified as having therapeutic potential if about a certain, or particular, percentage of cells of the enriched heterogeneous renal cell population are determined express the at least one (at least one, or at least two, or at least three, or at least four, or five) nephrogenic marker(s). The certain, particular, percentage of cells of the enriched heterogeneous renal cell population that may be determined to express the any at least one (at least one, or at least two, or at least three, or atleast four, or five) nephrogenic marker(s) may be any percentage for any of the nephrogenic markers as discussed earlier herein.

[0077] In these other methods, methods in which expression of TGF|32 by cells of the enriched heterogeneous renal cell population is determined, and optionally, the expression of at least one nephrogenic marker is determined, expression of at least one added marker may further be determined to identify the enriched heterogeneous renal cell population as having therapeutic potential. In instances where the at least one added marker may further be determined, the at least one added marker may be at least one (at least one, at least two, at least three or four) of gamma-glutamyl transpeptidase (GGT)-l, cytokeratin (CK)18, vascular endothelial growth factor (VEGF) or kidney injury molecule (KIM)-l. The at least one added marker may be GGT-1, or may be CK18, or may be VEGF, or may be KIM-1, or may be GGT-1 and CK18, or may be GGT-1 and VEGF, or may be GGT-1 and KIM-1, or may be CK-18 and VEGF, or may be CK18 and KIM-1, or may be VEGF and KIM-1, or may be GGT-1, CK18 and VEGF, or may be GGT-1, VEGF and KIM-1, or may be CK-18, VEGF and KIM-1, or may be GGT-1, CK-18 and KIM-1, or may be GGT-1, CK18, VEGF and KIM-1.

[0078] Determining that the cells of the enriched heterogeneous renal cell population further express the at least one added marker may identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0079] In some instances, the determining cells of the enriched heterogeneous renal cell population further express the at least one added marker may be a determining that a certain percentage of cells of the enriched heterogeneous renal cell population express the at least one added marker or may be a determining that cells of the enriched heterogeneous renal cell population secrete the at least one added marker. Determining that a certain percentage of cells of the enriched heterogeneous renal cell population express the at least one added marker, and / or that cells of the enriched heterogeneous renal cell population secrete the at least one added marker, may identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0080] In instances in which the at least one added marker is GGT-1, a certain percentage of cells of the enriched heterogeneous renal cell population may further be determined to express GGT-1 to identify the enriched heterogeneous renal cell population as having a therapeutic potential. In these instances, the percent cells that express GGT-1, that mayidentify the enriched heterogeneous renal cell population as having a therapeutic potential, may be greater than about 4%, greater than about 10%, greater than about 15%, greater than about 20%, greater than about 25%, greater than about 30%, greater than about 35%, greater than about 40%, greater than about 45% or greater than about 50%. Alternatively, the percent cells that express GGT-1, that may identify the enriched heterogeneous renal cell population as having a therapeutic potential, may be between about 4% and 85%, between about 4% and 82%, between about 4.5% and 80%, between about 4.5% and 75%, or between about 4.5% and 70%.

[0081] In instances in which the at least one added marker is CK18, a certain percentage of cells of the enriched heterogeneous renal cell population may further be determined to express CK18 to identify the enriched heterogeneous renal cell population as having a therapeutic potential. In these instances, the percent cells that express CK18 that may identify the enriched heterogeneous renal cell population as having a therapeutic potential may be greater than about 80%, greater than about 82%, greater than about 84%, greater than about 86%, greater than about 88%, greater than about 90%, greater than about 92%, greater than about 94%.

[0082] In instances in which the at least one added marker is VEGF and / or KIM-1, cells of the enriched heterogeneous renal cell population may further be determined to secrete VEGF and / or KIM-1 to identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0083] It should be understood that if the percentage of cells expressing a certain marker is provided as being a percentage of “about” a particular number e.g., about 5%, the percentage of cells need not be exactly the particular number, e.g., exactly 5%. Rather, it should be understood that if the percentage of cells expressing a certain marker is provided as being “about” a particular number, e.g., about 5%, then the percentage of cells expressing the certain marker may be within up to 10% of that particular number, e.g., between 4.5% and 5.5%. It should also be understood that if cells express a certain marker by secreting it at an amount of “about” a particular number, e.g., about 5 ng, the amount need not be exactly that particular number, e.g., exactly 5 ng. Rather, it should be understood that the secreted amount of the marker may be within 10% of the particular number, e.g., between 4.5 and 5.5 ng-

[0084] In any of the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, the determining whether cells of the enriched heterogeneous renal cell population express any marker(s), e.g., cell adhesion marker (ICAM5, MCAM, CNTNAP1, MMP2) nephrogenic marker (SIX1, RET, OSR1, LHX1 or FGF8), additional cell adhesion marker (COE11A1, PECAM1 or E-cadherin), further marker (e.g., TGF|32, nephrin, podocin, or RACK-1), TGFp2, or added marker (GGT1, CK18, VEGF or KIM-1), may be by detection of the marker(s) in a nucleic acid, e.g., mRNA or miRNA, or polypeptide form and may be by any suitable as say / technique. For example, if expression is determined in polypeptide form, it may be determined by assays such as Western blot, fluorescence activated cell sorting (FACS), enzyme linked immunosorbent assay (EEISA). If expression is determined in nucleic acid form, it may be determined by an assay such as, or that uses, Southern blot, polymerase chain reaction (PCR), or reverse transcriptase PCR, serial analysis of gene expression (SAGE), Mass ARRAY, or fluorescence in situ hybridization (FISH). Expression may be determined via a bulk or a single cell assay or may be determined after collection of conditioned media from a sample of cells from an enriched heterogeneous renal cell population. The assay may be one that employs a labeled detection reagent. The labeled detection reagent may include (a) a portion that complexes, directly or indirectly, with marker(s) and (b) a detection moiety. Non-limiting detection moieties include radioactive isotopes, e.g.,35S,14C,1251,3H and131I, colloidal gold particles, fluorescent labels, e.g., Texas Red, rhodamine, fluorescein, dansyl, Lissamine, phycocryterin, phycocyanin, SPECTRUM ORANGE, SPECTRUM GREEN1 and enzyme substrates, e.g., firefly luciferase, bacterial luciferase, luciferin, horseradish peroxidase, alkaline phosphatase, or beta galactosidase.

[0085] The enriched heterogeneous renal cell population, which may be identified as having a therapeutic potential in any of the methods, may be enriched for one or more renal cell types such as renal epithelial cells, renal tubular cells, renal tubular epithelial cells, or renal proximal tubular cells. The enrichment of the enriched heterogeneous renal cell population for these one or more of renal cell types may be a reference to the enriched heterogeneous renal cell population having a greater percentage of the one or more renal cell types than does a kidney tissue of a patient, a kidney biopsy of a patient, or an in vitro culture of cells established from a kidney tissue or kidney biopsy of a patient, (which, collectively, may be referred to as a “starting renal cell population”). A starting renal cell population, if an in vitro culture of cells established from a kidney tissue of a patient or a kidney biopsy of a patient,may be a renal cell preparation comprising dissociated cells of a kidney tissue or kidney biopsy (e.g., cells dissociated from the kidney tissue or kidney biopsy via mincing and / or enzyme digestion), that may or may not have been treated to remove red blood cells and debris. The enriched heterogeneous renal cell population, in addition to being enriched for renal epithelial cells, renal tubular cells, renal tubular epithelial cells, and / or renal proximal tubular cells, may also include other renal cell types such as glomerular cells, podocytes, collecting duct cells and / or vascular cells.

[0086] The enriched heterogeneous renal cell population may be enriched for the one or more renal cell types as a result of having been prepared from a starting renal cell population, (e.g., a kidney tissue of a patient, a kidney biopsy of a patient, or an in vitro culture of cells established from a kidney tissue or kidney biopsy of a patient), via a method that includes a separation step. The separation step may be one that separates cells of the starting renal cell population that have been passaged no more than one, two, or three times, on the basis of their buoyant density. If the separation step is one that separates cells on the basis of their buoyant density, the separation step may utilize a single or multi-step continuous or discontinuous density gradient using a density gradient media such as glycerol, glucose OptiPrep, Percoll, or Ficoll-Paque. The use of such a density gradient media in this manner may result in cells of the starting renal cell population (or starting renal cell population having been passaged at most one, two or three times) separating into one or more distinguishable fractions from which cells of the enriched heterogeneous renal cell population may be distinctly identified and isolated. The distinguishable fraction(s) may be one / those in which the buoyant density of cells in the fraction(s) is greater than about 1.045 g / mL, or greater than 1.045 g / mL, or greater than or equal to 1.045 g / mL. The distinguishable fraction(s) may be one / those in which the buoyant density of cells in the fraction(s) is greater than about 1.04 g / mL, or greater than 1.04 g / mL, or greater than or equal to 1.04 g / mL, or greater than about 1.0419 g / mL, or greater than 1.0419 g / mL, or greater than or equal to 1.0419 g / mL. The distinguishable fraction(s) may be one / those in which the buoyant density is between about 1.045 g / mL and about 1.091 g / mL, or between about 1.045 g / mL and about 1.052 g / mL. Alternatively, the separation step may be one that separates cells of the starting renal cell population (or cells of the starting renal cell population that have been passaged no more than one, two or three times), on the basis of whether they express particular markers on their surface. If the separation step separates cells on the basis of their expression of particular cell surface markers, the separation step may be one that utilizes flow cytometry.The flow cytometry may sort out cells from the starting renal cell population (or starting renal cell population having been passaged at most one, two or three times) if they express particular surface markers, such as nephrin or a cytokeratin (CK), e.g., CK18, characteristic of, e.g., renal epithelial cells, renal tubular cells, renal tubular epithelial cells, or renal proximal tubular cells, to thereby form the isolated enriched heterogeneous renal cell population.

[0087] The enriched heterogeneous renal cell population, having been prepared from a starting renal cell population (or starting renal cell population having been passaged at most one, two or three times) may be cultured under hypoxic conditions prior to the separation step. If the cells are cultured under hypoxic conditions prior to the separation step, the cells may be cultured under conditions in which the oxygen levels are less than about 20%, or less than about 15%, or less than about 10%, or less than about 9%, or less than about 8%, or less than about 7%, or less than about 6%, or less than about 5% oxygen, or less than about 4% oxygen, or less than about 3% oxygen or less than about 2% oxygen. If the cells are cultured under hypoxic conditions, the cells may be cultured under the hypoxic conditions for at least 6 hours, at least 8 hours, at least 10 hours, at least 12 hours, at least 14 hours, at least 16 hours, at least 20 hours, at least 24 hours, at least 30 hours, at least 36 hours, at least 42 hours, at least 48 hours, about 6 hours to about 48 hours, about 6 hours to about 36 hours, about 6 hours to about 24 hours, about 12 hours to about 48 hours, about 12 hours to about 36 hours, or about 12 hours to about 24 hours.

[0088] In general, the preparation of an enriched heterogeneous renal cell population may be from any starting cell population, for example, an in vitro culture of cells established from a kidney tissue of a patient or a kidney biopsy of a patient. If the enriched heterogeneous renal cell population is prepared from the in vitro culture of cells established from the kidney tissue or kidney biopsy of the patient, the cells of the in vitro culture may be expanded by passaging at most one, or at most two or at most three times. Alternatively, if desired, cells of the in vitro culture of cells established from the kidney tissue or kidney biopsy may be cryopreserved and then expanded by passaging at most one, or at most two or at most three times. Once the cells have been expanded, the expanded cells may be cryopreserved. The expanded cells, whether or not cryopreserved, may then be subject to a separation step or may then be subject to hypoxic culture conditions followed by a separation step. The enriched heterogeneous renal cell population is isolatable by having performed the separationstep. Once the enriched heterogeneous renal cell population has been isolated, it may be frozen and / or analyzed prior to use as a therapeutic.

[0089] If the enriched heterogeneous renal cell population is identified as having a therapeutic potential in accordance with any of the methods disclosed herein, it may be included in a pharmaceutical composition, or administered in a method of treating kidney disease in a patient in need thereof, and / or used in the manufacture of a medicament to treat kidney disease. If the enriched heterogeneous renal cell population is identified as having a therapeutic potential and is included in a pharmaceutical composition, it may be formulated as a hydrogel composition or as a liquid composition. The pharmaceutical composition may, or may not, include hyaluronic acid.

[0090] If the pharmaceutical composition is formulated as a hydrogel composition, cells of the enriched heterogeneous renal cell composition may be combined with a temperaturesensitive cell- stabilizing biomaterial. The temperature-sensitive cell- stabilizing biomaterial may be a biomaterial in a gel state at certain temperatures and a liquid state at others. For example, if the biomaterial is temperature- sensitive, the biomaterial may be in a gel state at about 8°C or below, a substantially liquid state at about ambient temperature or above, and a solid-to-liquid transitional state between about 8°C and about ambient temperature; or a gel state at about 4°C or below, a liquid state at about 37°C or above, and a solid-to-liquid transitional state between about 8°C and about 18°C; or a gel state at about 2°C or below, a liquid state at about 37 °C or above, and a solid-to-liquid transitional state between about 8 °C and about 18°C; or a gel state at about 2°C or below and a liquid state at about 37°C or above; or a gel state at about 4°C or below and a liquid state at about 34°C or above; or a gel state at about 6°C or below and a liquid state at about 32°C or above. The temperaturesensitive cell- stabilizing the biomaterial may include, or be made up of, one or more naturally sourced or recombinant proteins or peptides. The naturally sourced or recombinant proteins or peptides may be extracellular matrix proteins of recombinant origin, or extracellular matrix sourced from kidney or another tissue or organ, or gelatin. If the temperature-sensitive cellstabilizing biomaterial is, or includes, gelatin, the gelatin may be derived from a Type I, alpha I collagen such as porcine Type I, alpha I collagen or recombinant human Type I, alpha I collagen. If the temperature- sensitive cell-stabilizing biomaterial is, or includes, gelatin, the gelatin may present in the therapeutic composition at about 0.5% to about 1% weight per volume (w / v), or about 0.8% to about 0.9% (w / v), or about 0.75% (w / v) or about 0.88% (w / v). Cells of the enriched heterogeneous renal cell population may be dispersed throughoutthe biomaterial, or substantially uniformly distributed throughout the biomaterial. Cells of the enriched heterogeneous renal cell population may be formulated in the biomaterial, e.g., gelatin, such that the number of cells per mL biomaterial is about 20 x 106cells per mL, about 40 x 106cells per mL, about 60 x 106cells per mL, about 100 x 106cells per mL, about 120 x 106cells per mL, about 140 x 106cells per mL, about 160 x 106cells per mL, about 180 x 106cells per mL, or about 200 x 106cells per mL.

[0091] If the pharmaceutical composition is formulated as a liquid composition, the enriched heterogeneous renal cell population may be combined with any suitable liquid, e.g. appropriate cell storage or culture medium, a saline, or combinations thereof, for immediate use or for cryopreservation up until the timing of its use. If the therapeutic composition is a liquid composition, the cells of the enriched heterogeneous renal cell population may be suspended in a pharmaceutically acceptable carrier or excipient, such as saline, buffered saline, dextrose, water, polyethyleneglycol, and / or any combinations thereof. Cells of the enriched heterogeneous renal cell population may be combined with the suitable liquid, e.g., cell storage or culture medium, such that the number of cells per mL liquid is about 20 x 106cells per mL, about 40 x 106cells per mL, about 60 x 106cells per mL, about 100 x 106cells per mL, about 120 x 106cells per mL, about 140 x 106cells per mL, about 160 x 106cells per mL, about 180 x 106cells per mL, or about 200 x 106cells per mL.

[0092] If the enriched heterogeneous renal cell population is identified as having a therapeutic potential, the enriched heterogeneous renal cell population, or a pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be administered to a patient in a method of treating kidney disease or may be for use in a method of treating kidney disease. If the enriched heterogeneous renal cell population is identified as having a therapeutic potential, the enriched heterogeneous renal cell population, or a pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be used in the manufacture of a medicament to treat kidney disease. The kidney disease may be at any stage or degree of acute or chronic renal failure. The kidney disease may originate in the kidney or it may be secondary to another condition, e.g., heart failure, hypertension, diabetes, autoimmune disease or liver disease. Alternatively, the kidney disease may be a kidney disease arising from an acute injury to the kidney, or the result of an anomaly of the kidney and / or urinary tract. The kidney disease may further include endocrine dysfunctions such as anemia, e.g., erythropoietin-deficiency, and mineral imbalance, e.g., Vitamin D deficiency.

[0093] If the enriched heterogeneous renal cell population is identified as having a therapeutic potential, then administering the enriched heterogeneous renal cell population, or a pharmaceutical composition comprising the enriched heterogeneous renal cell population, may treat the kidney disease. It may treat the kidney disease by restoring kidney function, stabilizing kidney function, improving kidney function, reducing renal fibrosis or reducing renal inflammation in a kidney of a patient in need of such treatment. The treating the kidney disease may restore mineral balance, electrolyte balance, fluid homeostasis, reabsorption of essential nutrients, or Cystatin C metabolism, or alleviate anemia in a patient in need of such treatment. The treating the kidney disease may delay or prevent the need for dialysis, or it may delay or prevent the need for a kidney transplant in a patient in need of a treatment for kidney disease. If the treating the kidney disease delays the need for dialysis or the need for a kidney transplant in the patient, the delay may be by at least 1 year, at least 1.5 years, at least 2 years, at least 2.5 years, at least 3 years, at least 3.5 years, at least 4 years, at least 4.5 years, at least 5 years, at least 5.5 years, at least 6 years, at least 6.5 year, at least 7 years, at least 7.5 years, at least 8 years, at least 8.5 years, at least 9 years, at least 9.5 years or at least 10 years. The treating the kidney disease may be determined by observation in an improvement in the patient’s serum albumin, albumin to globulin ratio (A / G ratio), serum phosphorous, serum sodium, kidney size (measurable by ultrasound), serum calcium, phosphorous:calcium ratio, serum potassium, proteinuria, urine creatinine, serum creatinine, blood nitrogen urea (BUN), cholesterol levels, triglyceride levels and glomerular filtration rate (GFR), weight, blood pressure (mean systemic blood pressure, diastolic blood pressure, or systolic blood pressure), and physical endurance performance.

[0094] If the enriched heterogeneous renal cell population is identified as having a therapeutic potential, it may be administered to a patient by any suitable administration route known in the art. For instance, the enriched heterogeneous renal cell population, or a pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be systemically administered to a patient in need of treatment for kidney disease. The enriched heterogeneous renal cell population, or a pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be administered at or into the kidney(s) of a patient in need of treatment for kidney disease. If the enriched heterogeneous renal cell population is administered at or into the kidney(s) of the patient in need of treatment for kidney disease, it may be administered over a single or over multiple injection(s). It may be administered via direct laparotomy, via direct laparoscopy, transabdominally, orpercutaneously. The enriched heterogeneous renal cell population, or pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be administered by percutaneous injection into the renal cortex of a kidney, or may be administered by inserting a guiding cannula percutaneously to puncture the kidney capsule and then injecting the enriched heterogeneous renal cell population into the kidney. The enriched heterogeneous renal cell population, or pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be administered by injection into the renal cortex of one or both kidneys of the patient. The administration of the enriched heterogeneous renal cell population, or pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be by two injections wherein the first injection is into the renal cortex of one kidney and a second injection is into the renal cortex of the other kidney of the patient.

[0095] The enriched heterogeneous renal cell population, or pharmaceutical composition comprising the enriched heterogeneous renal cell population, may be administered by any suitable route, at a therapeutically effective dose. A therapeutically effective dose, or amount, for administration to the patient in need of treatment for kidney disease may include about 1-9 x 106enriched heterogeneous renal cell population cells per gram estimated kidney weight of the patient. A therapeutically effective amount of the pharmaceutical composition may be a dose of about 1.0 x 106, about 2.0 x 106, about 3.0 x 106, about 4.0 x 106, about 5.0 x 106, about 6.0 x 106, about 7.0 x 106, about 8.0 x 106, about 9.0 x 106, about 2.0 - 7.0 x 106, between about 4.0 - 7.0 x 106, or between about 5.0 x 106- 7.0 x 106cells of an enriched heterogeneous renal cell population per gram estimated kidney weight of the patient.

[0096] The administration of the therapeutic composition that includes the heterogeneous renal cell population to a patient in a method of treating kidney disease, may be by first and second injections. The first and second injections may be administered between approximately 3 and 12 months apart. The first and second injections may be administered approximately 3 months apart, approximately 4 months apart, approximately 5 months apart, approximately 6 months apart, approximately 7 months apart, approximately 8 months apart, approximately 9 months apart, approximately 10 months, approximately 11 months apart or approximately 12 months apart. The first and second injections may be administered between approximately 3 and 6 months apart, between approximately 6 and 9 months apart, between approximately 9 and 12 months apart, between approximately 3 and 9 months apart,between approximately 6 and 9 months apart or between approximately 6 and 12 months apart.

[0097] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. Such equivalents are intended to be encompassed by the appended claims.

[0098] All publications, patents and patent applications mentioned in this specification are herein incorporated by reference into the specification to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference in their entirety.EXAMPLESEXAMPLE 1 - Markers expressed by SRC population cells elucidate pathways by which they drive tubulogenic activity in the stabilization and restoration of kidney function in models for CKD

[0099] Introduction. Selected renal cells (SRCs) are an example of an enriched heterogeneous renal cell population, e.g., heterogeneous renal cell population enriched for renal epithelial cells. SRCs are being advanced as an autologous cell-based therapy for treatment of chronic kidney disease (CKD). SRC bioactivity has, in part, been attributed to a believed ability that they influence signaling cascades that mediate nephrogenesis or regeneration in the kidney; SRCs express certain markers expressed by kidney cells, e.g., uretic bud and cap mesenchyme cells, during kidney development or nephrogenesis. A study was conducted to determine whether human SRCs express other markers, such as cell adhesion markers, or secrete other factors, that further explain mechanisms by which they stabilize and restore kidney function in models for CKD.

[0100] Methods / Detection of Marker Expression by SRCs: Human SRCs (National Disease Research Interchange) were submitted to (i) mRNA-seq for identification of differentially expressed genes (DEGs; DEGs vs. source biopsy; Padj <0.05), (ii) scRNA-seq to map expression of genes and (iii) miRNAseq for analysis. SRC markers were identified using Gene Ontology (GO) and / or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and their network visualized using miRNet.ca.

[0101] Methods / scRNA-seq to Map Gene Expression: SRC aliquots were stained with acridine orange and propidium iodide and cells were assessed for viability, concentration, and singleness using the LUNA-FX7 Dual Fluorescence Cell Counter (Logos Biosystems). Cellswere then processed using the lOx Genomics Chromium Controller and the Chromium Single Cell 3' GEM, Library & Gel Bead Kit v3.1 Dual Index Kit (PN-1000268) following the manufacturer’s user guide (https: / / tinyurl . com / 4855859x). Briefly, approximately 5,000 cells per sample were loaded onto the Chromium Chip G with a target recovery of 3,000 cells per sample for library preparation. Single cells, reverse transcription reagents and gel beads coated with barcoded oligos were encapsulated together in an oil droplet to produce gel beads in emulsion (GEMs). Reverse transcription was performed using a C1000 thermal cycler (Bio-Rad) to generate complementary DNA (cDNA) libraries tagged with a cell barcode and unique molecular index (UMI). GEMs were then broken and cDNA was purified using Dynabeads MyOne SILANE beads (Invitrogen) prior to 12 cDNA amplification cycles. Amplified cDNA libraries were purified with SPRIselect magnetic beads (Beckman Coulter) and were quantified using an Agilent Bioanalyzer High Sensitivity DNA chip (Agilent Technologies). Fragmentation, end repair, A-tailing and double-sided size selection using SPRIselect beads were then performed. Illumina-compatible adapters were ligated onto the size-selected cDNA fragments. Adapter-ligated cDNA was then purified using SPRIselect beads. Uniquely identifiable indexes were added to this cDNA during 12 amplification cycles. The completed sequencing libraries were then purified using SPRIselect beads, visualized using the Bioanalyzer High Sensitivity DNA chip, and pooled in an equimolar ratio. Pooled libraries were sequenced on a NextSeq 2000 machine (Illumina) at the UNC High Throughput Sequencing Facility. Libraries were denatured and diluted following standard Illumina protocol, spiked with 1% PhiX sequencing control (Illumina), and sequenced on one P3 flow cell in paired-end format (Read 1: 28 cycles, i7 index: 10 cycles, i5 Index: 10 cycles, Read 2: 90 cycles) to a total depth of 1.2 billion read pairs passing quality filters. Demultiplexing and preliminary analysis were performed using Cell Ranger 7.1.0 with default settings. Analysis was performed using 10X Genomics’ Loupe Browser (Tables 1 and 2) or Seurat (Seurat, v5.0.1; Table 5).

[0102] Methods / Flow Cytometry Cell Surface Staining to Detect Protein Expression. SRCs were washed with, and resuspended to a concentration of 106 / mL in, flow buffer. 100 pl of the resuspended cells in flow buffer were pipetted into either wells of a 96 well round bottom plate or 5 mL 12x75 mm plastic tubes. If needed, an appropriate amount of Fc block was added to the wells / tubes for incubation at 4°C for 15 min. Conjugated monoclonal antibodies (clone WM59 for PECAM-1 (a.k.a. CD31) detection, clone HCD54 for ICAM-1 (a.k.a. CD54) detection, clone P1H12 for MCAM (a.k.a. CD146) detection, clone DECMA-1 for E-Cadherin (a.k.a. CDH1) detection), were next added, at pre-determined optimal concentrations, to the wells / tubes. The cells were incubated with the conjugated antibodies for 15 min at 4°C in the dark. Following incubation, the cells were washed 2x with 200 pl (plates) or 2 mL (tubes) cold flow buffer. The washed cells were incubated with an appropriate live / dead discriminator to exclude dead cells from subsequent analysis. The cells were then washed twice with ice cold flow buffer, suspended in 0.5 mL flow buffer and immediately read on a cytometer.

[0103] Methods / Detection of SRC TGF 32 Secretion: Secretion of TGF[32 by SRCs was determined by an enzyme-linked immunosorbent assay (ELISA) or an Intelliflex / Luminex assay. Briefly, cryopreserved SRCs were thawed and seeded at a density of 500,000 cells / well in a 6-well tissue culture plate. Twenty-four hours following seeding, the media was changed and new renal cell growth medium + 10 ng PMA (InSolution Phorbol-12- myristate-13-acetate, EMD Millipore, 5.00582.0001) was added to the cells for up to three days. Conditioned medium (supernatant) was collected on days 1, 2, and 3 and stored at - 80°C until performance of a TGF|32 ELISA or an Intelliflex / Luminex assay; in an initial assay, supernatant was collected at day 3 for use in the ELISA. The TGF[32 ELISA was performed in accordance with the Quantikine ELISA Human TGF-B2 kit (R&D Systems, DB-250) Manufacturer’s instructions. The TGF|32 Intelliflex / Luminex assay was performed using a Luminex TGF|3 triplex kit (R&D systems) and read on an xMAP Intelliflex reader. A medium only sample was used as a negative control.

[0104] Results / SRC Cell Adhesion Marker Expression: SRCs exhibited upregulation (Log2FC) of cell-cell adhesion genes icam5 (2.5), mcam (1.5), cntnapl (1.65), colllal (3.1) and mmp2 (2.1) and expression of PECAM1 and CDH1 (see, e.g., FIG. 1 and Table 1). Gene ontology confirmed an interactome comprising these cell-cell adhesion markers (see, e.g., FIG. 2).TABLE 1: Cell Adhesion Marker Expression by SRCs

[0105] Results / SRC TGF / 32 Expression'. In bulk miR analysis, when comparing SRCs to their source kidney biopsy tissue, hsa-miR-145-5p (log2FC=-6.9) and hsa-miR-199a-5p (log2FC=-5.7) were found to be downregulated in SRCs (padj<0.01). Gene ontology revealed that these miRNAs downregulate expression of tgfb2 together with renal epithelial markers (see, e.g., FIG. 3). Consistent with this observation, transcriptomic analysis confirmed upregulation of tgfb2 expression in SRCs (log2FC=2.5, padj <0.01), including in single cell analyses (see, e.g., Table 2 and FIG. 4). In EEISAs, SRCs were also found to secrete TGF[32 (FIG. 5A; n=3; p<0.01 vs media alone; TGF[32, range 300 pg / mE to 2000 pg / mE). SRCs TGF[32 secretion was time dependent (see, e.g., FIG. 5B and Table 3). TGF[32 secretion by SRCs was confirmed by a Intelliflex / Euminex assay, which is more sensitive than the EEISA (see, e.g., Table 4). Gene ontology revealed that tgfb2 forms an interactome with ret,fgf8, Ihxl, osrl and six2, ureteric bud and cap mesenchyme markers expressed by SRCs (see, e.g., FIG. 6 and Table 2), and GO BP analyses indicated this interactome is associated with epithelialization of filtrate components.TABLE 2: TGF|32, Uretic Bud and Cap Mesenchyme Marker Expression by SRCsTABLE 3: TGFp2 secretion by SRCs (ELISA)TABLE 4: TGF|32 secretion by SRCs (Intelliflex / Luminex)*For each cell sample, the assay was performed a first and second time, using first (1:6.4) and second (1:2.5) conditioned mediurmdiluent ratios. Detected ng TGF|32 per million cells is provided for each sample at each conditioned mediurmdiluent ratio (1:6.4 / 1:2.5).

[0106] Confirming SRCs tubulogenic activity, SRCs were placed in culture+hydrogel and stained for epithelial markers GGT and SCL12A1. SRCs assembled into tubules (see, e.g., FIG. 7A), and where found to stain positive for, e.g.. express, both GGT1 (see, e.g., FIG. 7B) and SCL12A1 (see, e.g., FIG. 7C).

[0107] Results / Further Analysis of SRC Cell Adhesion Marker Expression'. Additional SRC cell adhesion marker expression analyses were performed to confirm earlier studies. The additional analyses, scRNAseq analyses, were conducted using SRCs that had been prepared from tissue procured from the National Disease Research Interchange (NDRI) or from kidney biopsies of patients having type 2 diabetes (T2D) and chronic kidney disease (CKD) that were enrolled in one of two phase 2 clinical trials (002 (NCT02836574) and 007 (NCT05018416)), e.g., phase 2 clinical trials in which SRCs were under investigation as apotential cell therapeutic. Table 5 provides scRNAseq expression data for the cell adhesion markers.TABLE 5: Cell Adhesion Marker Expression by SRCs (scRNAseq)1Percent expression of each gene was calculated as the number of expressing SRCs out of the total number of SRCs of an aggregate of five patient SRC samples (total number of cells in the five, aggregate, patient samples = 28,555)Percent expression of each gene was calculated as the number of expressing SRCs out of the total number of SRCs of an aggregate of seventeen patient SRC samples (total number of cells in the seventeen, aggregate, patient samples = 204,216)

[0108] SRC surface protein expression of several of the cell adhesion markers was also analyzed by flow cytometry. PECAM, a.k.a. CD31, was detected on the surface of about 0.01% to about 0.24% of SRCs. ICAM, a.k.a. CD54, was detected on the surface of about 100% of SRCs (see, e.g., FIG. 8). MCAM, a.k.a. CD146, was detected on the surface of about 99.3% of SRCs. (see, e.g., FIG. 9). E-Cadherin, a.k.a. CDH1, was detected on the surface of about 0.1% of SRCs (see, e.g., FIG. 10). A summary of the surface expression data of the above adhesion markers from three (PK018, PK019, and HK025) SRC samples is provided in Table 6 below.TABLE 6. SRC cell adhesion molecules (% positive)

[0109] Taken together, SRC gene expression data presented herein has elucidated mechanisms by which SRCs may mediate regenerative and restorative activity in diseasedkidneys. Expression of uretic bud markers, ret and fgf8, and cap mesenchyme markers, six2, osrl, and Ihxl , ret, have identified SRCs as cells potentially able to recapitulate events associated with embryologic kidney development. The identification of SRCs’ TGF / 32 and cell adhesion marker expression suggests that among SRCs potential therapeutic activities is an ability to drive formation of, or to form, renal tubules, possibly resulting in improved maintenance of electrolyte balance, fluid homeostasis, reabsorption of essential nutrients, urine concentration and Cystatin C metabolism in a kidney disease setting.

[0110] While the disclosure has been particularly shown and described with reference to specific embodiments (some of which are preferred embodiments), it should be understood by those having skill in the art that various changes in form and detail can be made therein without departing from the spirit and scope of the present disclosure as disclosed herein. There is no intention, therefore, of limitations to the exact abstract and disclosure herein presented.

Claims

CLAIMS1. A method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, comprising: determining whether cells of the enriched heterogeneous renal cell population express at least one cell adhesion marker, wherein the at least one cell adhesion marker comprises one or more of: intercellular adhesion molecule 5 (ICAM5), melanoma cell adhesion molecule (MCAM), contactin associated protein 1 (CNTNAP1), or matrix metallopeptidase 2 (MMP2); and identifying the enriched heterogeneous renal cell population as having therapeutic potential if cells of the enriched heterogeneous renal cell population are determined to express the at least one cell adhesion marker.

2. The method of claim 1, wherein the step of determining comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one cell adhesion marker.

3. The method of claim 1, wherein the at least one cell adhesion marker comprises ICAM5.

4. The method of claim 2, wherein the at least one cell adhesion marker comprises ICAM5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5.

5. The method of claim 2, wherein the at least one cell adhesion marker comprises ICAM5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5.

6. The method of claim 1, wherein the at least one cell adhesion marker comprises MCAM.

7. The method of claim 2, wherein the at least one cell adhesion marker comprises MCAM, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM.

8. The method of claim 2, wherein the at least one cell adhesion marker comprises MCAM, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM.

9. The method of claim 1, wherein the at least one cell adhesion marker comprises CNTNAP1.

10. The method of claim 2, wherein the at least one cell adhesion marker comprises CNTNAP1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1.

11. The method of claim 2, the at least one cell adhesion marker comprises CNTNAP1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1.

12. The method of claim 1, wherein the at least one cell adhesion marker comprises MMP2.

13. The method of claim 2, wherein the at least one cell adhesion marker comprises MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 8% and at most about14. The method of claim 2, wherein the at least one cell adhesion marker comprises MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

15. The method of claim 2, wherein the at least one cell adhesion marker comprises MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 15% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

16. The method of claim 1, wherein the at least one cell adhesion marker comprises:(a) ICAM5 and MCAM; or(b) ICAM5 and CNTNAP1; or(c) ICAM5 and MMP2; or(d) MCAM and CNTNAP1; or(e) MCAM and MMP2; or(f) CNTNAP1 and MMP2.

17. The method of claim 2, wherein the at least one cell adhesion marker comprises:(a) ICAM5 and MCAM, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM; or(b) ICAM5 and CNTNAP1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1; or(c) ICAM5 and MMP2, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2; or(d) MCAM and CNTNAP, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM and greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP; or(e) MCAM and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM and greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2; or(f) CNTNAP 1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP and greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2.

18. The method of claim 2, wherein the at least one cell adhesion marker comprises:(a) ICAM5 and MCAM, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM; or(b) ICAM5 and CNTNAP 1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells ofthe enriched heterogeneous renal cell population express ICAM5 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1; or(c) ICAM5 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5 and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2; or(d) MCAM and CNTNAP, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP 1; or(e) MCAM and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2; or(f) CNTNAP 1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1 and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

19. The method of claim 1, wherein the at least one cell adhesion marker comprises:(a) ICAM5, MCAM and CNTNAP1; or(b) ICAM5, MCAM and MMP2; or(c) ICAM5, CNTNAP1 and MMP2; or(d) MCAM, CNTNAP 1 and MMP2.

0. The method of claim 2, wherein the at least one cell adhesion marker comprises:(a) ICAM5, MCAM and CNTNAP1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM and greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1; or(b) ICAM5, MCAM and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM and greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2; or(c) ICAM5, CNTNAP1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1 and greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2; or(d) MCAM, CNTNAP1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM, greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP and greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2.

1. The method of claim 2, wherein the at least one cell adhesion marker comprises:(a) ICAM5, MCAM and CNTNAP1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1; or(b) ICAM5, MCAM and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2; or(c) ICAM5, CNTNAP1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2; or(d) MCAM, CNTNAP1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

22. The method of claim 1, wherein the at least one cell adhesion marker comprises ICAM5, MCAM, CNTNAP1 and MMP2.

23. The method of claim 2, wherein the at least one cell adhesion marker comprises ICAM5, MCAM, CNTNAP1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 0% and at most about 0.5% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express MCAM, greater than about 4% and at most about 15% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and greater than about 8% and at most about 25% of cells of the enriched heterogeneous renal cell population express MMP2.

24. The method of claim 2, wherein the at least one cell adhesion marker comprises ICAM5, MCAM, CNTNAP1 and MMP2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 60% of cells of the enriched heterogeneous renal cell population express ICAM5, greater than about 65% of cells of the enriched heterogeneous renal cell population express MCAM, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express CNTNAP1, and greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express MMP2.

25. The method of any preceding claim further comprising: determining whether cells of the enriched heterogeneous renal cell population express at least one nephrogenic marker, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is further determined that cells of the enriched heterogeneous renal cell population express the at least one nephrogenic marker, wherein the at least one nephrogenic marker comprises one or more of: homeobox protein sine oculis homeobox homolog 2 (SIX2), rearranged during transfection (RET), odd-skipped related 1 (OSR1), lim homeobox protein 1 (LHX1), or fibroblast growth factor 8 (FGF8).

26. The method of claim 25, wherein the determining whether the cells of the enriched heterogeneous renal cell population express the at least one nephrogenic marker comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one nephrogenic marker.

27. The method of claim 25, wherein the at least one nephrogenic marker comprises SIX2.

28. The method of claim 26, wherein the at least one nephrogenic marker comprises SIX2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6.0% of cells of the enriched heterogeneous renal cell population express SIX2.

29. The method of claim 25, wherein the at least one nephrogenic marker comprises OSR1.

30. The method of claim 26, wherein the at least one nephrogenic marker comprises OSR1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1.

31. The method of claim 25, wherein the at least one nephrogenic marker comprises LHX1.

32. The method of claim 26, wherein the at least one nephrogenic marker comprises LHX1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and most about 58% of cells of the enriched heterogeneous renal cell population express LHX1.

33. The method of claim 25, wherein the at least one nephrogenic marker comprises RET.

34. The method of claim 26, wherein the at least one nephrogenic marker comprises RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET.

35. The method of claim 25, wherein the at least one nephrogenic marker comprises FGF8.

36. The method of claim 26, wherein the at least one nephrogenic marker comprises FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

37. The method of claim 25, wherein the at least one nephrogenic marker comprises:(a) SIX2 and OSR1; or(b) SIX2 and LHX1; or(c) SIX2 and RET; or(d) SIX2 and FGF8; or(e) OSR1 and LHXl; or(f) OSR1 and RET; or(g) OSR1 and FGF8; or(h) LHX1 and RET; or(i) LHX1 and FGF8; or(j) RET and FGF8.

38. The method of claim 26, wherein the at least one nephrogenic marker comprises:(a) SIX2 and OSR1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1; or(b) SIX2 and LHXl, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1; or(c) SIX2 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(d) SIX2 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(e) OSR1 and LHX1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1; or(f) OSR1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(g) OSR1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express0SR1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(h) LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(i) LHX1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(j) RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

39. The method of claim 25, wherein the at least one nephrogenic marker comprises:(a) SIX2, OSR1 and LHX1; or(b) SIX2, OSR1 and RET; or(c) SIX2, OSR1 and FGF8; or(d) SIX2, LHX1 and RET; or(e) SIX2, LHX1 and FGF8; or(f) SIX2, RET and FGF8; or(g) OSR1, LHX1 and RET; or(h) OSR1, LHX1 and FGF8; or(i) OSR1, RET and FGF8; or(j) LHX1, RET and FGF8.

0. The method of claim 26, wherein the at least on nephrogenic marker comprises:(a) SIX2, OSR1 and EHX1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express EHX1; or(b) SIX2, OSR1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(c) SIX2, OSR1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(d) SIX2, LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(e) SIX2, LHX1 and FGF8, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6.0% of cells of the enriched heterogeneous renal cell population express SIX2, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(f) SIX2, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(g) OSR1, LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(h) OSR1, LHX1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(i) OSR1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at mostabout 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(j) EHXl, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express EHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

41. The method of claim 25, wherein the at least one nephrogenic marker comprises:(a) SIX2, OSR1, LHX1 and RET; or(b) SIX2, OSR1, LHX1 and FGF8; or(c) SIX2, LHX1, RET and FGF8; or(d) SIX2, OSR1, RET and FGF8; or(e) OSR1, LHX1, RET and FGF8.

42. The method of claim 26, wherein the at least one nephrogenic marker comprises:(a) SIX2, OSR1, LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET;(b) SIX2, OSR1, LHX1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at mostabout 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8;(c) SIX2, LHX1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8;(d) SIX2, OSR1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8;(e) OSR1. LHX1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

43. The method of claim 25, wherein the at least one nephrogenic marker comprises SIX2, OSR1, LHX1, RET and FGF8.

44. The method of claim 26, wherein the at least one nephrogenic marker comprises SIX2, OSR1, LHX1, RET and FGF, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express EHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

45. The method of any preceding claim further comprising: determining whether cells of the enriched heterogeneous renal cell population express at least one additional cell adhesion marker, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that cells of the enriched heterogeneous renal cell population express the at least one additional cell adhesion marker, wherein the at least one additional cell adhesion marker comprises: collagen type XI alpha 1 (COE11A1), platelet endothelial cell adhesion molecule (PEC AM) 1 or E- cadherin.

46. The method of claim 45, wherein the determining whether the cells of the enriched heterogeneous renal cell population express the at least one additional cell adhesion marker comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one additional cell adhesion marker.

47. The method of claim 46, wherein the at least one additional cell adhesion marker comprises COL11A1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 20% and at mostabout 55% of cells of the enriched heterogeneous renal cell population express COL11A1.

48. The method of claim 46, wherein the at least one additional cell adhesion marker comprises C0L11A1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 20% and at most about 40% of cells of the enriched heterogeneous renal cell population express COL11A1.

49. The method of claim 46, wherein the at least one additional cell adhesion marker comprises COL11A1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 25% and at most about 55% of cells of the enriched heterogeneous renal cell population express COL11A1.

50. The method of any of claims 46-49, wherein the at least one additional cell adhesion marker comprises PECAM1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 0.1% and at most about 0.4% of cells of the enriched heterogeneous renal cell population express PECAM1.

51. The method of any of claims 46-50, wherein the at least one additional cell adhesion marker comprises E-cadherin, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and at most about 35% of cells of the enriched heterogeneous renal cell population express E- cadherin.

52. The method of any of claims 46-50, wherein the at least one additional cell adhesion marker comprises E-cadherin, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 15% and at most about 35% of cells of the enriched heterogeneous renal cell population express E- cadherin.

53. The method of any of claim 46-50, wherein the at least one additional cell adhesion marker comprises E-cadherin, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express E-cadherin.

54. The method of any preceding claim, further comprising: determining whether cells of the enriched heterogeneous renal cell population express transforming growth factor beta 2 ( TG F[32), wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that cells of the enriched heterogeneous renal cell population express TGF[32.

55. The method of claim 54, wherein the determining whether the cells of the enriched heterogeneous renal cell population express TGF[32 comprises determining percentage of cells of the enriched heterogeneous renal cell population that express TGF[32.

56. The method of claim 55, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 50% of cells of the enriched heterogeneous renal cell population express TGF[32.

57. The method of claim 54, wherein the determining whether the cells of the enriched heterogeneous renal cell population express TGF[32 comprises determining whether cells of the enriched heterogeneous renal cell population secrete TGF[32.

58. The method of claim 57, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that an amount of at least about 1.0 ng TGF[32 is secreted per 1,000,000 enriched heterogeneous renal cell population cells.

59. The method of claim 57, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that an amount of at least about 2.0 ng TGF[32 is secreted per 1,000,000 enriched heterogeneous renal cell population cells.

60. The method of claim 57, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that an amount of at least about 2.4 ng TGF[32 is secreted per 1,000,000 enriched heterogeneous renal cell population cells.

61. The method of claim 57, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that about 3.0 ng to about 20 ng TGF[32 is secreted per 1,000,000 enriched heterogeneous renal cell population cells.

62. The method of any preceding claim, further comprising: determining whether cells of the enriched heterogeneous renal cell population express at least one further marker, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that cells of the enriched heterogeneous renal cell population express the at least one further marker, wherein the at least one further marker comprises nephrin, podocin or receptor for activated C kinase (RACK-1).

63. The method of claim 62, wherein the determining whether the cells of the enriched heterogeneous renal cell population express the at least one further marker comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one further marker.

64. The method of claim 63, wherein the at least one further marker comprises nephrin, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 4% and at most about 99% of cells of the heterogeneous renal cell population express nephrin.

65. The method of claim 63, wherein the at least one further marker comprises podocin, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 90% of cells of the heterogeneous renal cell population express podocin.

66. The method of claim 63, wherein the at least one further marker comprises RACK-1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that at least about 85% of cells of the heterogeneous renal cell population express RACK-1.

67. A method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, comprising: determining expression of TGF[32 by cells of the enriched heterogenous renal cell population; and identifying the enriched heterogeneous renal cell population as having therapeutic potential if it is determined that:(i) greater than about 50% of cells of the enriched heterogeneous renal cell population express TGF[32; and / or(ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 1.0 ng per 1 ,000,000 enriched heterogeneous renal cell population cells.

68. The method of claim 67, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that: (i) greater than about 50% of cells of the enriched heterogeneous renal cell population express TGF[32.

69. The method of claim 68, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that between about 50% and about 80% of cells of the enriched heterogeneous renal cell population express TGF[32.

70. The method of claim 67, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that: (ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 1.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

71. The method of claim 70, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 2.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

72. The method of claim 71, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 2.4 ng per 1,000,000 enriched heterogeneous renal cell population cells.

73. The method of claim 72, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 3.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

74. The method of claim 73, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of about 3.0 ng to about 20 ng per 1,000,000 enriched heterogeneous renal cell population cells.

75. The method of claim 67, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that: (ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about .7 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 24- hour time period.

76. The method of claim 75, wherein the amount is at least about 2.0 ng per 1,000,000 enriched heterogeneous renal cell population cells over the approximate 24-hour time period.

77. The method of claim 67, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that: (ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 3.5 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 48- hour time period.

78. The method of claim 67, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is determined that: (ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 8.0 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 72- hour time period.

79. The method of claim 68 or 69, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is further determined that: (ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 1.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

80. The method of claim 68 or 69, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is further determined that: (ii) TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 2.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

81. The method of claim 68 or 69, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is further determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of at least about 3.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

82. The method of claim 68 or 69, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is further determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of about 3.0 ng to about 20 ng per 1,000,000 enriched heterogeneous renal cell population cells.

83. The method of claim 65 or 69, wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if it is further determined that TGF[32 is secreted by cells of the enriched heterogeneous renal cell population in an amount of: at least about .7 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 24-hour time period; at least about 3.5 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 48 -hour time period; and / or at least about 8.0 ng per 1,000,000 enriched heterogeneous renal cell population cells over an approximate 72-hour time period.

84. The method of claim 83, wherein the amount TGF[32 secreted by cells of the enriched heterogeneous renal cell population over the approximate 24-hour time period is at least about 2.0 ng per 1,000,000 enriched heterogeneous renal cell population cells.

85. The method of claim 84, wherein the amount TGF[32 secreted by cells of the enriched heterogeneous renal cell population over the approximate 24-hour time period is at least about 2.5 ng per 1,000,000 enriched heterogeneous renal cell population cells.

86. The method of any of claims 67-85 further comprising determining whether cells of the enriched heterogeneous renal cell population express: at least one nephrogenic marker, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that cells of the enriched heterogeneous renal cell population express the at least one nephrogenic marker,wherein the at least one nephrogenic marker comprises one or more of: SIX2, RET, OSR1, LHX1, or FGF8.

87. The method of claim 86, wherein the determining whether the cells of the enriched heterogeneous renal cell population express the at least one nephrogenic marker comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one nephrogenic marker.

88. The method of claim 86 wherein the at least one nephrogenic marker comprises SIX2.

89. The method of claim 87, wherein the at least one nephrogenic marker comprises SIX2, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6.0% of cells of the enriched heterogeneous renal cell population express SIX2.

90. The method of claim 86, wherein the at least one nephrogenic marker comprises OSR1.

91. The method of claim 87, wherein the at least one nephrogenic marker comprises OSR1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1.

92. The method of claim 86, wherein the at least one nephrogenic marker comprises EHX1.

93. The method of claim 87, wherein the at least one nephrogenic marker comprises EHX1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and most about 58% of cells of the enriched heterogeneous renal cell population express EHX1.

94. The method of claim 86, wherein the at least one nephrogenic marker comprises RET.

95. The method of claim 87, wherein the at least one nephrogenic marker comprises RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET.

96. The method of claim 86, wherein the at least one nephrogenic marker comprises FGF8.

97. The method of claim 87, wherein the at least one nephrogenic marker comprises FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

98. The method of claim 86, wherein the at least one nephrogenic marker comprises:(a) SIX2 and OSR1; or(b) SIX2 and LHX1; or(c) SIX2 and RET; or(d) SIX2 and FGF8; or(e) OSR1 and LHXl; or(f) OSR1 and RET; or(g) OSR1 and FGF8; or(h) LHX1 and RET; or(i) LHX1 and FGF8; or(j) RET and FGF8.

99. The method of claim 87, wherein the at least one nephrogenic marker comprises:(a) SIX2 and OSR1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1; or(b) SIX2 and LHXl, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1; or(c) SIX2 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(d) SIX2 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(e) OSR1 and LHX1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1; or(f) OSR1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(g) OSR1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express0SR1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(h) LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(i) LHX1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(j) RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

100. The method of claim 86, wherein the at least one nephrogenic marker comprises:(a) SIX2, OSR1 and LHX1; or(b) SIX2, OSR1 and RET; or(c) SIX2, OSR1 and FGF8; or(d) SIX2, LHX1 and RET; or(e) SIX2, LHX1 and FGF8; or(f) SIX2, RET and FGF8; or(g) OSR1, LHX1 and RET; or(h) OSR1, LHX1 and FGF8; or(i) OSR1, RET and FGF8; or(j) LHX1, RET and FGF8.

01. The method of claim 87, wherein the at least on nephrogenic marker comprises:(a) SIX2, OSR1 and EHX1, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express EHX1; or(b) SIX2, OSR1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(c) SIX2, OSR1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(d) SIX2, LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(e) SIX2, LHX1 and FGF8, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6.0% of cells of the enriched heterogeneous renal cell population express SIX2, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(f) SIX2, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(g) OSR1, LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET; or(h) OSR1, LHX1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(i) OSR1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at mostabout 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8; or(j) EHXl, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express EHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

102. The method of claim 86, wherein the at least one nephrogenic marker comprises:(a) SIX2, OSR1, LHX1 and RET; or(b) SIX2, OSR1, LHX1 and FGF8; or(c) SIX2, LHX1, RET and FGF8; or(d) SIX2, OSR1, RET and FGF8; or(e) OSR1, LHX1, RET and FGF8.

103. The method of claim 87, wherein the at least one nephrogenic marker comprises:(a) SIX2, OSR1, LHX1 and RET, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET;(b) SIX2, OSR1, LHX1 and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at mostabout 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1 and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8;(c) SIX2, LHX1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8;(d) SIX2, OSR1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8;(e) OSR1. LHX1, RET and FGF8, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express LHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

104. The method of claim 86, wherein the at least one nephrogenic marker comprises SIX2, OSR1, LHX1, RET and FGF8.

105. The method of claim 87, wherein the at least one nephrogenic marker comprises SIX2, OSR1, EHX1, RET and FGF, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is further determined that greater than 0% and at most about 6% of cells of the enriched heterogeneous renal cell population express SIX2, greater than 0% and at most about 85% of cells of the enriched heterogeneous renal cell population express OSR1, greater than about 8% and at most about 58% of cells of the enriched heterogeneous renal cell population express EHX1, greater than 0% and at most about 90% of cells of the enriched heterogeneous renal cell population express RET and greater than 0% and at most about 59% of cells of the enriched heterogeneous renal cell population express FGF8.

106. An enriched heterogeneous renal cell population identified according to the method of any of claims 1-105.

107. A pharmaceutical composition comprising the enriched heterogeneous renal cell population of claim 106.

108. A method of treating kidney disease in a patient in need thereof, the method comprising: administering a therapeutically effective amount of the pharmaceutical composition of claim 107.

109. Use of the pharmaceutical composition of claim 107 in the manufacture of a medicament to treat kidney disease.

110. The enriched heterogenous renal cell population of claim 106, wherein the population is prepared via a method comprising a step of density gradient separation.

111. The enriched heterogenous renal cell population of claim 110, wherein the population comprises cells of a buoyant density greater than about 1.04 g / mL.

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