Selected renal cell population cells, 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. In some embodiments, it includes 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: (i) ureteric bud and / or cap mesenchyme (UB / CM) marker; and / or (ii) podocyte marker.

Description

SELECTED RENAL CELL POPULATION CELLS, CHARACTERISTICS AND USES THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 589,937, filed on October 12, 2023, and U.S. Provisional Patent Application Serial No. 63 / 652,522, filed on May 28, 2024. The disclosures of the above-referenced applications are herein expressly incorporated by reference in their entireties, including any drawings.BACKGROUND

[0002] The incidence and prevalence of chronic kidney disease (CKD) are increasing given the growing diabetes and metabolic syndrome epidemics (Thurlow JS, et al., Am J Nephrol. 2021; 52:98-107). Left untreated, CKD can progress to end-stage renal disease (ESRD) and necessitate the need for renal replacement therapy. Dialysis, associated with increased morbidity and mortality, not only remains a bridge to transplantation but also represents a significant burden on the federal health exchequer (Thurlow JS, et al., Am J Nephrol. 2021; 52:98-107; Murphy D, et al., Intern Med 2016; 65:473-481; Hill NR, et al., PLoS One 77:e0158765. doi: 10.1371 / joumal.pone.0158765; Glassock RJ, et al., Nat Rev Nephrol. 2017; 75:104-114; Migliori M, et al., J Nephrol. 2017, 50:373-383). Considering that patients often become refractory to therapeutic regimen addressing disease etiology there is urgent need for modalities that repair renal microarchitecture, restore kidney function, and delay or avert the need for dialysis.

[0003] Autologous cell therapy employs an individual’s cells, which typically are cultured and expanded outside the body, and then re-introduced into the individual. Advantages of such an approach include reduced risks for alloimmune events, bioincompatibility, and disease transmission (Kazmi B, et al., Wounds 2009; 9:234-242). Autologous selected renal cell (SRC) therapy utilizes biopsy-sourced kidney cells, a select fraction of which are implanted into the donor’s kidney (Stavas J, et al., KI Reports 2022; 7:1619-1629; Stavas J, et al., Blood Purif. 2023; 52:114-121). Phenotype-labeling studies suggest that SRCs express ureteric bud (UB), cap mesenchyme (CM) and podocyte makers (Stavas J, et al., KI Reports 2022; 7:1619-1629) suggesting that these cells have renal reparative and restorative potential. In diabetic kidney disease (DKD) cohorts at increased risk for ESRD, randomization to SRCs(REACT™) may be associated with stabilization of renal function (Stavas J, et al., KI Reports 2022; 7:1619-1629; Stavas J, et al., Blood Purif. 2023; 52:114-121).

[0004] There is a need in the art to identify heterogeneous renal cell populations, such as SRCs, with potential therapeutic activity, e.g., via a renal reparative and restorative ability, that could delay or prevent a CKD patient's progress to ESRD.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: (i) ureteric bud and / or cap mesenchyme (UB / CM) marker; and / or (ii) podocyte marker. The at least one UB / CM marker includes one or more of: Wingless-related integration site family member 11 (WNT11), Gremlin (GREM)l, E26 transformation-specific (ETS) variant transcription 5 (ETV5), Homeobox (HOX)ll, or neural cell adhesion molecule (NCAM)l. The at least one podocyte marker includes one or more of thrombospondin type 1 domain containing (THSD)7A, protein tyrosine phosphatase receptor type O (PTPRO), matrix metalloproteinase (MPP)5, tubulin polymerization promoting protein (TPPP)3, or lim homeobox transcription factor 1 beta (LMX1B). 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: (i) UB / CM marker and / or (ii) podocyte marker.

[0006] The present disclosure describes a further method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential. Percentages of renal cells of the population expressing genes characteristic of ureteric bud, cap mesenchyme, and podocyte cells are determined. The renal cell population is identified as having a therapeutic potential if it is determined that: (i) between about 20% and about 40% of renal cells of the population express genes characteristic of ureteric bud and cap mesenchyme cells; and (ii) ) between about 50% and about 65% of renal cells of the population express genes characteristic of podocyte cells. The population is prepared from non-fetal renal tissue.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIG. 1: Shows diameter size (pm) of human SRC-derived organoids cultured over 18 days.

[0008] FIGS. 2A-2D: Show images of immunofluorescent antibody stained human SRC- derived organoids. Organoid expression of ureteric bud+cap mesenchyme cell markers (Hoxall (FIG. 2B), CK8 (FIG. 2C) and Meis2 (FIG. 2D)) was detected. FIG. 2A, organoids stained with an isotype matched antibody control.

[0009] FIGS. 3A-3B. Show images of immunofluorescent antibody stained human SRC- derived organoids. Organoid expression of glomerular epithelium markers (Thds7a (FIG.3 A) and Ptpro (FIG. 3B)) was detected.

[0010] FIGS. 4A-4B: Show images of immunofluorescent antibody stained human SRC- derived organoids. Organoid expression of proximal tubule markers (LTL (FIG. 4A) and CD 13 (FIGs. 4A and 4B)) was detected.

[0011] FIGS. 5A-5B: Show images of immunofluorescent antibody stained human SRC- derived organoids. Organoid expression of epithelial cell division cycle marker Cdc6 (FIG. 5A) was detected. FIG. 5B, organoids stained with an isotype matched antibody control.

[0012] FIGS. 6A-6B: Show images of sectioned, periodic acid Schiff (PAS)-stained 8-day (FIG. 6 A) and 17 -day (FIG. 6B) cultured human SRC-derived organoids. At 8 days in culture, structures having a glomerulus-like appearance, including a parietal epithelial cell (PEC)-like rim (FIG. 6A, arrows), were observed. At 17 days in culture, structures exhibiting nephron-like features, including glomerular tuft-like structures (FIG. 6B, arrows), were observed.

[0013] FIGS. 7A-7B: Show tubular structural features (FIG. 7A inside rectangle) in images of sectioned, periodic acid Schiff (PAS)-stained 17-day cultured human SRC-derived organoids. FIG. 7B, magnification of area inside rectangle in FIG. 7A.

[0014] FIG. 8. Shows an opnl^\-cavl-mmp9-icaml-cxcr4 axis, uncovered by Gene ontology, that regulates renal migration, cell-cell adhesion, and wound healing.

[0015] FIG. 9: Shows genes and / or proteins expressed by SRCs and by cells during stages of kidney development.

[0016] FIG. 10: Shows the shared podocyte-PEC and SRC transcriptome.

[0017] FIG. 11 : Uniform manifold approximation and projection (UMAP) showing that SRCs express hesl. Navy / darker grey dots represent cells that express hesl. Light grey dots represent cells that do not express hesl. The majority of cells, approximately 90%, in this particular SRC population expressed hesl.DETAILED DESCRIPTION

[0018] The present disclosure relates generally to are methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, a composition including an enriched heterogeneous renal cell population identified as having a therapeutic potential, and methods and uses of an enriched heterogeneous renal cell population identified as having a therapeutic potential.

[0019] 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.

[0020] 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 methods may 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.

[0021] 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: (i) UB / CM marker; and / or (ii) podocyte marker. In some instances, the at least one marker may be the (i) UB / CM marker. In instances in which the at least one marker is the at least one UB / CM marker, the at least one UB / CM marker may be, or include, any of Wingless-related integration site family member 11 (WNT11), Gremlin (GREM)l, E26 transformation-specific (ETS) variant transcription 5 (ETV5), Homeobox (HOX)ll or neural cell adhesion molecule (NCAM)l. In some instances, in which the at least one marker is the at least one UB / CM marker, the at least one UB / CM marker may be two or more of WNT11, GREM1, ETV5, HOX11, and / orNCAM1 . The at least two UB / CM markers may be, or include: (a) WNT11 and GREM1 ;(b) WNT11 and ETV5; (c) WNT11 and HOX11; (d) WNT11 andNCAMl; (e) GREM1 and ETV5; (f) GREM1 and HOX11; (g) GREM1 and NCAM1; (h) ETV5 and HOX11; (i) ETV5 and NCAM1 ; or (j) HOX11 and NCAM1. In other instances, in which the at least one marker is the at least one UB / CM marker, the at least one UB / CM marker may be any three or more of WNT11, GREM1, ETV5, HOX11 and / or NCAM1. The at least three UB / CM markers may be, or include: (a) WNT11, GREM1 and ETV5; (b) WNT11, GREM1 and HOX1 1 ; (c) WNT11 , GREM1 and NCAM1 ; (d) WNT11 , ETV5 and HOX11 ; (e) WNT11 , ETV5 and NCAM1; (f) WNT11, HOX11 and NCAM1; (g) GREM1, ETV5 and HOXll;(h) GREM1, ETV5 andNCAMl; (i) GREM1, HOX11 andNCAMl; or (j) ETV, HOX11 and NCAM1 . In other instances, instances in which the at least one marker is the at least one UB / CM marker, the at least one UB / CM marker may be any four or more of WNT11, GREM1, ETV5, HOX11 and / or NCAM1. The at least four UB / CM markers may be, or include: (a) WNT11 , GREM1 , ETV5 and HOX11 ; (b) WNT11 , GREM1 , ETV5 and NCAM1; (c) WNT11, ETV5, HOX11 andNCAMl; (d) WNT11, GREM1, HOX11 and NCAM1; or (e) GREM1, ETV5, HOX11 and NCAM1. In yet other instances, instances in which the at least one marker is the at least one UB / CM marker, the at least one UB / CM marker may be, or include, WNT11, GREM1, ETV5, HOX11, and / or NCAM1.

[0022] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, methods in which it may be determined whether cells of the enriched heterogeneous renal cell population express at least one: (i) UB / CM marker; and / or (ii) podocyte marker, the at least one marker may be a (ii) podocyte marker. In instances in which the at least one marker is the at least one podocyte marker, the at least one podocyte marker may be, or include, any of thrombospondin type 1 domain containing (THSD)7A, protein tyrosine phosphatase receptor type O (PTPRO), matrix metalloproteinase (MPP)5, tubulin polymerization promoting protein (TPPP)3, lim homeobox transcription factor 1 beta (LMX1B). In some instances, instances in which the at least one marker is the at least one podocyte marker, the at least one podocyte marker may be two or more of THSD7A, PTPRO, MPP5, TPPP3 or LMX1B. The two or more podocyte markers may be, or include: (a) THSD7A and PTPRO; (b) THSD7A and MPP5; (c) THSD7A and TPPP3; (d) THSD7A and LMX1B; (e) PTPRO and MPP5; (f) PTPRO and TPPP3; (g) PTPRO and LMX1B; (h) MPP5 and TPPP3; (i) MPP5 and LMX1B; or (j) TPPP3 and LMX1B. In other instances, instances in which the at least one marker is the at least one podocyte marker, the at least one podocytemarker may be any three or more of THSD7A, PTPRO, MPP5, TPPP3 or LMX1B. The three or more podocyte markers may be, or include: (a) THSD7A, PTPRO and MPP5; (b) THSD7A, PTPRO and TPPP3; (c) THSD7A, PTPRO and LMX1B; (d) THSD7A, MPP5and TPPP3; (e) THSD7A, MPP5and LMX1B; (f) THSD7A, TPPP3and LMX1B; (g) PTPRO, MPP5and TPPP3; (h) PTPRO, MPP5 and LMX1B; (i) PTPRO, TPPP3 and LMX1B; or (j) MPP5, TPPP3and LMX1B. In other instances, instances in which the at least one marker is the at least one podocyte marker, the at least one podocyte marker may be any four or more of THSD7A, PTPRO, MPP5, TPPP3 or LMX1B. The four or more podocyte markers may be, or include: (a) THSD7A, PTPRO, MPP5 and TPPP3; (b) THSD7A, PTPRO, MPP5 and LMX1B; (c) THSD7A, MPP5, TPPP3 and LMX1B; (d) THSD7A, PTPRO, TPPP3 and LMX1B; or (e) GREM1, MPP5, TPPP3 and LMX1B. In yet other instances, instances in which the at least one marker is the at least one podocyte marker, the at least one podocyte marker may be, or include, THSD7A, PTPRO, MPP5, TPPP3 or LMX1B.

[0023] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, methods in which it may be determined whether cells of the enriched heterogeneous renal cell population express at least one (i) UB / CM marker; and / or (ii) podocyte marker, the at least one marker may include both (i) one or more UB / CM marker and (ii) one or more podocyte marker. In these instances of the methods, the at least one UB / CM marker may be, or include, any one, any combination of two, any combination of three, any combination of four, or all five of WNT11, GREM1, ETV5, HOX11 and / or NCAM1, e.g., as set forth earlier herein, and the at least one podocyte marker may be, or include, any one, any combination of two, any combination of three, any combination of four, or all five of THSD7A, PTPRO, MPP5, TPPP3 or LMX1B, e.g., as set forth herein.

[0024] In these methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, determining that cells of the heterogeneous enriched renal cell population express the: (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker may identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0025] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, the determining expression of the: (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one,at least two, at least three, at least four or five) podocyte marker may farther include determining percentage of cells of the enriched heterogeneous renal cell population that express the: (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker. If the percentage of cells of the enriched heterogeneous renal cell population that express the: (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if about a certain, or particular, percentage of cells of the enriched heterogeneous renal cell population express the: (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker.

[0026] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express WNT11 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 0%, greater than 0% and at most about 10%, greater than 0% and at most about 7.5%, greater than 0% and at most about 5%, greater than 0% and at most about 2.5%, greater than 0% and at most about 2.0%, greater than 0% and at most about 1.5%, greater than 0% and at most about 1.0%, 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%, or greater than 0% and at most about .1% of cells of the enriched heterogeneous renal population are determined to express WNT11.

[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 GREM1 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 0%, greater than 0% and at most about 12%, greater than 0% and at most about 10%, 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%, or greater than 0% and at most about 2.5% of cells of the enriched heterogeneous renal population are determined to express GREM1.

[0029] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express GREM1 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 5% and at most about 50%, greater than 5% and at most about 45%, greater than 5% and at most about 40%, greater than 5% and at most about 35%, greater than 5% and at most about 30%, greater than 5% and at most about 25%, greater than 5% and at most about 20%, greater than 5% and at most about 15%, or greater than 5% and at most about 10% of cells of the enriched heterogeneous renal population are determined to express GREM1.

[0030] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express ETV5 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 2%, greater than about 2% and at most about 30%, greater than about 2% and at most about 25%, greater than about 2% and at most about 20%, greater than 3%, greater than about 3% and at most about 30%, greater than about 3% and at most about 25%, greater than about 3% and at most about 20%, greater than 4%, greater than about 4% and at most about 30%, greater than about 4% and at most about 25%, greater than about 4% and at most about 20% of cells of the enriched heterogeneous renal population are determined to express ETV5.

[0031] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express ETV5 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 50% and at most about 60%, greater than about 50% and at most about 65%, greater than about 50% and at most about 70%, greater than about 50% and at most about 75%, greater than about 55% and at most about 60%, greater than about 55% and at most about 65%, greater than about 55% and at most about 70%, greater than about 55% and at most about 75%, greaterthan about 60% and at most about 65%, greater than about 60% and at most about 70%, or greater than about 60% and at most about 75% of cells of the enriched heterogeneous renal population are determined to express ETV5.

[0032] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express HOX11 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 1%, greater than about 1% and at most about 25%, greater than about 1% and at most about 20%, greater than about 1% and at most about 15%, greater than about 1% and at most about 12.5%, greater than about 2%, greater than about 2% and at most about 25%, greater than about 2% and at most about 20%, greater than about 2% and at most about 15%, greater than about 2% and at most about 12.5%, greater than 2.5%, greater than about 2.5% and at most about 25%, greater than about 2.5% and at most about 20%, greater than about 2.5% and at most about 15%, greater than about 2.5% and at most about 12.5%, greater than about 3%, greater than about 3% and at most about 25%, greater than about 3% and at most about 20%, greater than about 3% and at most about 15%, or greater than about 3% and at most about 12.5% of cells of the enriched heterogeneous renal population are determined to express HOX11.

[0033] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express HOX11 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 10%, greater than about 10% and at most about 20%, greater than about 10% and at most about 25%, greater than about 10% and at most about 30%, greater than about 10% and at most about 35%, greater than about 15%, and at most about 20%, greater than about 15% and at most about 25%, greater than about 15% and at most about 30%, greater than about 15% and at most about 35%, greater than about 17.5% and at most about 20%, greater than about 17.5% and at most about 25%, greater than about 17.5% and at most about 30%, greater than about 17.5% and at most about 35%, greater than about 20% and at most about 25%, greater than about 20% and at most about 30%, or greater than about 20% and at most about 35% of cells of the enriched heterogeneous renal population are determined to express HOX11.

[0034] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express NCAM1 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 0%, greater than 0% and at most about 5%, greater than 0% and at most about 4%, greater than 0% and atmost 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 1.9%, greater than 0% and at most about 1.8%, greater than 0% and at most about 1.7%, greater than 0% and at most about 1.6%, greater than 0% and at most about 1.5%, greater than about .25%, greater than about .25% and at most about 5%, greater than about .25% and at most about 4%, greater than about .25% and at most about 3%, greater than about .25% and at most about 2.5%, greater than about .25% and at most about 2%, greater than about .25% and at most about 1.9%, greater than about .25% and at most about 1.8%, greater than about .25% and at most about 1.7%, greater than about .25% and at most about 1.6%, greater than about .25% and at most about 1.5% of cells of the enriched heterogeneous renal population are determined to express NCAM1.

[0035] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express NCAM1 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than .5% and at most about 4%, greater than .5% and at most about 5%, greater than .5% and at most about 6%, greater than .5% and at most about 7%, greater than .5% and at most about 8%, greater than .5% and at most about 9%, greater than .5% and at most about 10%, greater than about 1% and at most about 4%, greater than about 1% and at most about 5%, greater than about 1% and at most about 6%, greater than about 1% and at most about 7%, greater than about 1% and at most about 8%, greater than about 1% and at most about 9%, greater than about 1% and at most about 10%, greater than about 1.5% and at most about 4%, greater than about 1.5% and at most about 5%, greater than about 1.5% and at most about 6%, greater than about 1.5% and at most about 7%, greater than about 1.5% and at most about 8%, greater than about 1.5% and at most about 9%, or greater than about 1.5% and at most about 10% of cells of the enriched heterogeneous renal population are determined to express NCAM1.

[0036] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express THSD7A is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about .5%, greater than about .5% and at most about 15%, greater than about .5% and at most about 12.5%, greater than about .5% and at most about 10%, greater than about .5% and at most about 8%, greater than about .5% and at most about 7%, greater than about .5% and at most about 6%, greater than about .5% and at most about 5%, greater than about .5% and at most about 4%, greater than about 1%, greater than about 1% and at most about 15%, greater than about 1% and at most about 12.5%, greater than about 1% and at most about 10%, greaterthan about 1% and at most about 8%, greater than about 1% and at most about 7%, greater than about 1% and at most about 6%, greater than about 1% and at most about 5%, greater than about 1% and at most about 4%, greater than about 1.5%, greater than about 1.5% and at most about 15%, greater than about 1.5% and at most about 12.5%, greater than about 1.5% and at most about 10%, greater than about 1.5% and at most about 8%, greater than about 1.5% and at most about 7%, greater than about 1.5% and at most about 6%, greater than about 1.5% and at most about 5%, greater than about 1.5% and at most about 4%, greater than about 2%, greater than about 2% and at most about 15%, greater than about 2% and at most about 12.5%, greater than about 2% and at most about 10%, greater than about 2% and at most about 8%, greater than about 2% and at most about 7%, greater than about 2% and at most about 6%, greater than about 2% and at most about 5%, or greater than about 2% and at most about 4% of cells of the enriched heterogeneous renal population are determined to express THSD7A.

[0037] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express THSD7A 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 50%, greater than about 5% and at most about 45%, greater than about 5% and at most about 40%, greater than about 5% and at most about 35%, greater than about 5% and at most about 30%, greater than about 5% and at most about 25%, greater than about 5% and at most about 20%, 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 10% and at most about 35%, greater than about 10% and at most about 30%, greater than about 10% and at most about 25%, greater than about 10% and at most about 20%, greater than about 15% and at most about 50%, greater than about 45% and at most about 40%, greater than about 15% and at most about 35%, greater than about 15% and at most about 30%, greater than about 15% and at most about 25%, or greater than about 15% and at most about 20% of cells of the enriched heterogeneous renal population are determined to express THSD7A.

[0038] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express PTPRO is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 0%, 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 2.5%, greater than 0% and at most about2%, greater than 0% and at most about 1.9%, greater than 0% and at most about 1.8%, greater than 0% and at most about 1.7%, greater than 0% and at most about 1.6%, greater than 0% and at most about 1.5%, greater than about .1%, greater than about .1% and at most about 5%, greater than about .1% and at most about 4%, greater than about .1% and at most about 3%, greater than about .1% and at most about 2.5%, greater than about .1% and at most about 2%, greater than about .1% and at most about 1.9%, greater than about .1% and at most about 1.8%, greater than about .1% and at most about 1.7%, greater than about .1% and at most about 1.6%, greater than about .1% and at most about 1.5%, greater than about .2%, greater than about .2% and at most about 5%, greater than about .2% and at most about 4%, greater than about .2% and at most about 3%, greater than about .2% and at most about 2.5%, greater than about .2% and at most about 2%, greater than about .2% and at most about 1.9%, greater than about .2% and at most about 1.8%, greater than about .2% and at most about 1.7%, greater than about .2% and at most about 1.6%, greater than about .2% and at most about 1.5%, greater than about .3%, greater than about .3% and at most about 5%, greater than about .3% and at most about 4%, greater than about .3% and at most about 3%, greater than about .3% and at most about 2.5%, greater than about .3% and at most about 2%, greater than about .3% and at most about 1.9%, greater than about .3% and at most about 1.8%, greater than about .3% and at most about 1.7%, greater than about .3% and at most about 1.6%, or greater than about .3% and at most about 1.5% of cells of the enriched heterogeneous renal population are determined to express PTPRO.

[0039] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express PTPRO is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 2% and at most about 15%, greater than 2% and at most about 14%, greater than 2% and at most about 13%, greater than 2% and at most about 12%, greater than 2% and at most about 11%, greater than 2% and at most about 10%, greater than 2% and at most about 9%, greater than 2% and at most about 8%, greater than 2% and at most about 7%, greater than 2% and at most about 6%, greater than 2% and at most about 5%, greater than about 2.5% and at most about 15%, greater than about 2.5% and at most about 14%, greater than about 2.5% and at most about 13%, greater than about 2.5% and at most about 12%, greater than about 2.5% and at most about 11%, greater than about 2.5% and at most about 10%, greater than about 2.5% and at most about 9%, greater than about 2.5% and at most about 8%, greater than about 2.5% and at most about 7%, greater than about 2.5% and at most about 6%, greater than about 2.5%and at most about 5%, greater than about 3% and at most about 15%, greater than about 3% and at most about 14%, greater than about 3% and at most about 13%, greater than about 3% and at most about 12%, greater than about 3% and at most about 11%, greater than about 3% and at most about 10%, greater than about 3% and at most about 9%, greater than about 3% and at most about 8%, greater than about 3% and at most about 7%, greater than about 3% and at most about 6%, or greater than about 3% and at most about 5% of cells of the enriched heterogeneous renal population are determined to express PTPRO.

[0040] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express MPP5 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 25%, greater than about 25% and at most about 75%, greater than about 25% and at most about 70%, greater than about 25% and at most about 65%, greater than about 25% and at most about 60%, greater than about 30%, greater than about 30% and at most about 75%, greater than about 30% and at most about 70%, greater than about 30% and at most about 65%, greater than about 30% and at most about 60%, greater than about 35%, greater than about 35% and at most about 75%, greater than about 35% and at most about 70%, greater than about 35% and at most about 65%, greater than about 35% and at most about 60%, greater than about 40%, greater than about 40% and at most about 75%, greater than about 40% and at most about 70%, greater than about 40% and at most about 65%, greater than about 40% and at most about 60%, greater than about 45%, greater than about 45% and at most about 75%, greater than about 45% and at most about 70%, greater than about 45% and at most about 65%, or greater than about 45% and at most about 60% of cells of the enriched heterogeneous renal population are determined to express MPP5.

[0041] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express MPP5 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than about 70% and at most about 99%, greater than about 70% and at most about 95%, greater than about 70% and at most about 90%, greater than about 70% and at most about 85%, greater than about 70% and at most about 80%, greater than about 75% and at most about 99%, greater than about 75% and at most about 95%, greater than about 75% and at most about 90%, greater than about 75% and at most about 85%, greater than about 75% and at most about 80%, greater than about 80% and at most about 99%, greater than about 80% and at most about 95%, greater than about 80% and at most about 90%, greater than about 80% and at mostabout 85%, greater than about 85% and at most about 99%, greater than about 85% and at most about 95%, greater than about 85% and at most about 90%, greater than about 90% and at most about 99%, or greater than about 90% and at most about 95% of cells of the enriched heterogeneous renal population are determined to express MPP5.

[0042] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express TPPP3 is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 0%, 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 .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 about .1%, greater than about .1% and at most about 5%, greater than about .1% and at most about 4%, greater than about .1% and at most about 3%, greater than about .1% and at most about 2%, greater than about .1% and at most about 1%, greater than about .1% and at most about .9%, greater than about .1% and at most about .8%, greater than about .1% and at most about .7%, greater than about .1% and at most about .6%, greater than about .1% and at most about .5%, greater than about .1% and at most about .4%, greater than about .2%, greater than about .2% and at most about 5%, greater than about .2% and at most about 4%, greater than about .2% and at most about 3%, greater than about .2% and at most about 2%, greater than about .2% and at most about 1%, greater than about .2% and at most about .9%, greater than about .2% and at most about .8%, greater than about .2% and at most about .7%, greater than about .2% and at most about .6%, greater than about .2% and at most about .5%, or greater than about .2% and at most about .4% of cells of the enriched heterogeneous renal population are determined to express TPPP3.

[0043] In the methods, if the percentage of cells of the enriched heterogeneous renal cell population that express LMX1B is determined, then the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if greater than 0%, 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 .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 .25%, or greater than 0% and at most about .2% of cells of the enriched heterogeneous renal population are determined to express LMX1B.

[0044] 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 (any one, at least two, at least three, at least four or five) UB / CM marker 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 determined: (i) greater than 0% of cells of the enriched heterogeneous renal cell population express WNT11, (ii) greater than 0% of cells of the enriched heterogeneous renal cell population express GREM1, (iii) greater than about 2% and at most about 30% of cells of the enriched heterogeneous renal cell population express ETV5; (iv) greater than about 1% and at most about 25% of cells of the enriched heterogeneous renal cell population express HOX11; and / or (v) greater than 0% of the enriched heterogeneous renal cell population express NCAM1 . 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 (any one, at least two, at least three, at least four or five) UB / CM marker 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 determined: (i) greater than 0% and at most about 1% of cells of the enriched heterogeneous renal cell population express WNT11, (ii) greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1, (iii) greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, (iv) greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11 and / or (v) greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1.

[0045] In instances of the methods in which the percentage of cells of the enriched heterogeneous renal cell population that express the at least one (any one, at least two, at least three, at least four or five) UB / CM marker 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 determined: (i) greater than 0% of cells of the enriched heterogeneous renal cell population express WNT11, (ii) greater than about 5% and at most about 50% of cells of the enriched heterogeneous renal cell populationexpress GREM1, (iii) greater than about 50% and at most about 75% of cells of the enriched heterogeneous renal cell population express ETV5; (iv) greater than about 10% and at most about 35% of cells of the enriched heterogeneous renal cell population express HOX11; and / or (v) greater than about .5% and at most about 10% of the enriched heterogeneous renal cell population express NCAM1. 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 (any one, at least two, at least three, at least four or five) UB / CM marker is fiirther 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 determined: (i) greater than 0% and at most about 1% of cells of the enriched heterogeneous renal cell population express WNT11, (ii) greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, (iii) greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, (iv) greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11 and / or (v) greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1.

[0046] 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 WNT11 and GREM1; WNT11 and ETV5; WNT11 and HOXll; WNT11 andNCAMl; GREM1 and ETV5; GREM1 and HOXll; GREM1 and NCAMl; ETV5 and HOXll; ETV5 andNCAMl; HOX1 1 and NCAM1 ; WNT11 , GREM1 and ETV5; WNT11 , GREM1 and HOX11 ; WNT11 , GREM1 andNCAMl; WNT11, ETV5 and HOXll; WNT11, ETV5 and NCAMl; WNT11, HOX11 and NCAMl; GREM1, ETV5 and HOXll; GREM1, ETV5 and NCAMl; GREM1, HOX11 and NCAMl; ETV, HOX11 andNCAMl; WNT11, GREM1, ETV5 and HOXll; WNT11, GREM1, ETV5 andNCAMl; WNT11, ETV5, HOX11 andNCAMl; WNT11, GREM1, HOX11 and NCAMl; GREM1, ETV5, HOX11 and NCAMl; or WNT11, GREM1, ETV5, HOX11 andNCAMl.

[0047] In some instances of these examples of the methods, in addition to determining certain percentages of cells of the enriched heterogeneous renal cell population that express the any two, any three, any four, or all five UB / CM markers to identify the enriched heterogeneous renal cell population as having a therapeutic potential, it may be also determined whether the cells of the enriched heterogeneous renal cell population express at least one (any one, at leasttwo, at least three, at least four or five) podocyte markers to identify the enriched heterogeneous renal cell population as having a therapeutic potential. Alternatively, in addition to determining certain percentages of cells of the enriched heterogeneous renal cell population that express the any two, any three, any four, or all five UB / CM markers to identify the enriched heterogeneous renal cell population as having a therapeutic potential, it may also be determined whether a certain percentage of cells of the enriched heterogeneous renal cell population express the at least one (any one, at least two, at least three, at least four or five) podocyte markers to identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0048] 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 (any one, at least two, at least three, at least four or five) podocyte marker 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 determined: (i) greater than about .5% and at most about 15% of cells of the enriched heterogeneous renal cell population express THSD7A; (ii) greater than 0% of cells of the enriched heterogeneous renal cell population express PTPRO; (iii) greater than about 25% and at most about 75% of cells of the enriched heterogeneous renal cell population express MPP5; (iv) greater than 0% of cells of the enriched heterogeneous renal cell population express TPPP3 and / or (v) greater than 0% of cells of the enriched heterogeneous renal cell population express LMX1B. 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) podocyte marker 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 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A; (ii) greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO; (iii) greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5; (iv) greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3; and / or (v) greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

[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 (any one, at least two, at least three, at least four or five) podocyte marker 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 determined: (i) greater than about 5% and at most about 50% of cells of the enriched heterogeneous renal cell population express THSD7A; (ii) greater than 2% and at most about 15% of cells of the enriched heterogeneous renal cell population express PTPRO; (iii) greater than about 70% and at most about 99% of cells of the enriched heterogeneous renal cell population express MPP5; (iv) greater than 0% of cells of the enriched heterogeneous renal cell population express TPPP3 and / or (v) greater than 0% of cells of the enriched heterogeneous renal cell population express LMX1B. 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) podocyte marker 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 fiirther determined: (i) greater than about 10% and at most about 30% of cells of the enriched heterogeneous renal cell population express THSD7A; (ii) greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO; (iii) greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5; (iv) greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3; and / or (v) greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

[0050] 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 THSD7A and PTPRO; THSD7A and MPP5; THSD7A and TPPP3; THSD7A and LMX1B; PTPRO and MPP5; PTPRO and TPPP3; PTPRO and LMX1B; MPP5 and TPPP3; MPP5 and LMX1B; TPPP3 and LMX1B; THSD7A, PTPRO and MPP5; THSD7A, PTPRO and TPPP3;THSD7A, PTPRO and LMX1B; THSD7A, MPP5 and TPPP3; THSD7A, MPP5 and LMX1B; THSD7A, TPPP3 and LMX1B; PTPRO, MPP5 and TPPP3; PTPRO, MPP5 and LMX1B; PTPRO, TPPP3 and LMX1B; MPP5, TPPP3 and LMX1B; THSD7A, PTPRO, MPP5 and TPPP3; THSD7A, PTPRO, MPP5 and LMX1B; THSD7A, MPP5, TPPP3 andLMX1B; THSD7A, PTPRO, TPPP3 and LMX1B; GREM1, MPP5, TPPP3 and LMX1B; or THSD7A, PTPRO, MPP5, TPPP3, and LMX1B.

[0051] In some instances of these examples of the methods, in addition to determining certain percentages of cells of the enriched heterogeneous renal cell population that express the any two, any three, any four, or all five podocyte markers to identify the enriched heterogeneous renal cell population as having a therapeutic potential, it may be also determined whether the cells of the enriched heterogeneous renal cell population express at least one (any one, at least two, at least three, at least four or five) UB / CM markers to identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0052] In the methods of determining an enriched heterogeneous renal cell population has a therapeutic potential, in addition to determining whether cells of the enriched heterogeneous renal cell population express the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker, the expression of at least one further marker may be detected. The at least one further marker may be a further UB / CM marker such as rearranged during transfection (RET), fibroblast growth factor (FGF)8, FGF10, cbp / P300 interacting transactivator (CITED) 1, eyes absent (EYA)l, sine oculis homeobox homolog 2 (SIX2), oddskipped related 1 (OSR1) and / or glial cell derived neurotrophic factor (GDNF). The determining the expression of the at least one further marker with the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker, may identify the enriched heterogeneous renal cell population as having a therapeutic potential.

[0053] In the methods of determining an enriched heterogeneous renal cell population has a therapeutic potential, in addition to determining whether cells of the enriched heterogeneous renal cell population express the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker and, optionally, (iii) one or more further marker(s), it may additionally be determined whether cells of the enriched heterogeneous renal cell population express at least one added marker, where the at least one added marker may be a further podocyte marker, e.g., nphsl (podocin). The determining the expression of the at least one added marker with the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least fouror five) podocyte marker and, optionally, (iii) one or more further marker(s) may identify the enriched heterogeneous renal cell population as having therapeutic potential.

[0054] In the methods of determining an enriched heterogeneous renal cell population has a therapeutic potential, in addition to determining whether cells of the enriched heterogeneous renal cell population express the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker and, optionally, (iii) one or more further and / or added marker(s), it may additionally be determined whether cells of the enriched heterogeneous renal cell population express at least one podocyte-PEC marker. The podocyte-PEC marker may be, or include, hesl or CD44. The determining the expression of the at least one podocyte-PEC marker with the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker and, optionally, (iii) at least one or more fiirther and / or added marker(s) may identify the enriched heterogeneous renal cell population as having therapeutic potential.

[0055] In instances of the method in which it is further determined whether cells of the enriched heterogeneous renal cell population express the podocyte-PEC marker, and the podocyte-PEC marker is hesl, the determining whether cells of the enriched heterogeneous renal cell population express hesl may be a determination that a certain percentage of the cells of the enriched heterogeneous renal cell population express hesl. If, in instances of the method where it is further determined that a certain percentage of the cells of the enriched heterogeneous renal cell population express hesl, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is further determined that greater than about 65%, greater than about 65% and at most about 98%, greater than about 65% and at most about 95%, greater than about 65% and at most about 90%, greater than about 70%, greater than about 70% and at most about 98%, greater than about 70% and at most about 95%, greater than about 70% and at most about 90%, greater than about 75%, greater than about 75% and at most about 98%, greater than about 75% and at most about 95%, greater than about 75% and at most about 90%, greater than about 80%, greater than about 80% and at most about 98%, greater than about 80% and at most about 95%, or greater than about 80% and at most about 90% of cells of the enriched heterogeneous renal cell population express hesl.

[0056] Furthermore, in the methods of determining an enriched heterogeneous renal cell population has a therapeutic potential, in addition to determining whether cells of the enriched heterogeneous renal cell population express the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker; and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker and, optionally, (iii) one or more further and / or added marker(s), and, optionally, (iv) the at least one podocyte-PEC marker, it may also be determined whether cells of the enriched heterogeneous renal cell population express transforming growth factor beta 2 (TGF02). If it is determined that cells of the enriched heterogeneous renal cell population express TGF02 in addition to the (i) at least one (any one, at least two, at least three, at least four or five) UB / CM marker(s); and / or (ii) at least one (any one, at least two, at least three, at least four or five) podocyte marker and, optionally, (iii) at least one or more further and / or added marker(s) and, optionally, (iv) the at least one podocyte-PEC marker, the enriched heterogeneous renal cell population may be identified as having therapeutic potential.

[0057] In instances of the method in which it is further determined whether cells of the enriched heterogeneous renal cell population express TGF02, the determining whether cells of the enriched heterogeneous renal cell population may be a determination that a certain percentage of the cells of the enriched heterogeneous renal cell population express TGF02 or may be a determination that cells of the enriched heterogeneous renal cell population secrete a certain amount of TGF02. In these instances, the enriched heterogeneous renal cell population may be identified as having therapeutic potential if it is further determined that a certain percentage of cells express TGF02 or a certain amount of TGF02 is secreted by cells of the enriched heterogeneous renal cell population, respectively.

[0058] If, in instances of the method where it is further determined that a certain percentage of the cells of the enriched heterogeneous renal cell population express TGF02, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that greater than 40%, 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 45%, 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 50%, 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 mostabout 70%, greater than 55%, greater than about 55% and at most about 85%, greater than about 55% and at most about 80%, greater than about 55% and at most about 75%, or greater than about 55% and at most about 80% of cells of the enriched heterogeneous renal cell population express TGF02.

[0059] If, in instances of the method in which it is further determined that cells of the enriched heterogeneous renal cell population secrete a certain amount of TGF02, the enriched heterogeneous renal cell population may be identified as having a therapeutic potential if it is determined that cells of the enriched heterogeneous renal cell population secrete 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, or greater than about 6.5 ng, or greater than about 7.0 ng, or greater than about 7.5 ng, or greater than about 8.0 ng, or greater than about 8.5 ng, or greater than about 9.0, or greater than about 9.5 ng TGF02 per million cells. The TGF02 secreted by the cells of the enriched heterogeneous renal cell population in these amounts, may be in culture media over 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, between about 24 hours and about 48 hours, or between about 48 hours and about 72 hours.

[0060] In another method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential provided by the disclosure, percentages of renal cells of the enriched heterogeneous renal cell population that express genes characteristic of UB, CM and podocyte cells may be determined. The enriched heterogeneous renal cell population may be determined as having a therapeutic potential if it is determined that: (i) between about 20% and about 40% of renal cells of the population express genes characteristic of ureteric bud and cap mesenchyme cells; and (ii) between about 50% and about 65% of renal cells of the population express genes characteristic of podocyte cells. In these methods, the renal cell population is prepared from non-fetal renal tissue.

[0061] In such methods of the disclosure, the heterogeneous renal cell population may be determined as having a therapeutic potential if (i) between about 15% and about 50%, between about 15% and about 48%, between about 15% and about 46%, between about 15% and about 44%, between about 15% and about 42%, between about 15% and about 40%, between about 17.5% and about 50%, between about 17.5% and about 48%, between about 17.5% and about 46%, between about 17.5% and about 44%, between about 17.5% and about 42%, between about 17.5% and about 40%, between about 20% and about 50%, between about 20% and about 48%, between about 20% and about 46%, between about 20% and about 44%, between about 20% and about 42%, or between about 20% and about 40% of cells of the population express genes characteristic of ureteric bud and cap mesenchyme cells; and (ii) between about 45% and about 75%, between about 45% and about 70%, between about 45% and about 65%, between about 45% and about 60%, between about 50% and about 75%, between about 50% and about 70%, between about 50% and about 65%, between about 50% and about 60%, between about 55% and about 75%, between about 55% and about 70%, between about 55% and about 65%, or between about 55% and about 60% of cells of the population express genes characteristic of podocyte cells.

[0062] In some instances of these methods, the heterogeneous renal cell population may be determined as having a therapeutic potential if (i) between about 15% to about 50% of cells of the population express genes characteristic of ureteric bud and cap mesenchyme cells and (ii) between about 45% and about 75% of cells of the population express genes characteristic of podocyte cells. In other instances of these methods, the heterogeneous renal cell population may be determined as having a therapeutic potential if (i) between about between about 17.5% to about 46% of cells of the population express genes characteristic of ureteric bud and cap mesenchyme cells and (ii) between about 45% and about 70% of cells of the population express genes characteristic of podocyte cells. In yet other instances, the heterogeneous renal cell population may be determined as having a therapeutic potential if (i) between about 20% and about 40% of renal cells of the population express genes characteristic of ureteric bud and cap mesenchyme cells; and (ii) between about 50% and about 65% of renal cells of the population express genes characteristic of podocyte cells. In further other instances, the heterogeneous renal cell population may be determined as having a therapeutic potential if (i) between about 20% and about 40% of renal cells of the population express genes characteristic of ureteric bud and cap mesenchyme cells; and (ii)between about 55% and about 65% of renal cells of the population express genes characteristic of podocyte cells.

[0063] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, where the percentages of renal cells of the enriched heterogeneous renal cell population that express genes characteristic of UB, CM and podocyte cells are determined, the genes characteristic of UB and CM cells may be, or include, Wingless-related integration site family member 11 (WNT11), Gremlin (GREM)l, E26 transformation-specific (ETS) variant transcription 5 (ETV5), Homeobox (HOX)ll, neural cell adhesion molecule (NCAM)l, rearranged during transfection (RET), fibroblast growth factor 8 (FGF8), FGF10, cbp / P300 interacting transactivator (CITED)l, eyes absent (EYA)l, sine oculis homeobox homolog 2 (SIX2), odd-skipped related 1 (OSR1), and glial cell derived neurotrophic factor (GDNF). Alternatively, the genes characteristic of UB and CM cells may consist of WNT11, GREM1, ETV5, HOX11, NCAM1, RET, FGF8, FGF10, CITED1, EYA1, SIX2, OSR1, and GDNF.

[0064] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, where the percentages of renal cells of the enriched heterogeneous renal cell population that express genes characteristic of UB, CM, and podocyte cells may be determined, the genes characteristic of podocyte cells may be, or include, matrix metalloproteinase (MPP)5. Alternatively, the genes characteristic of the podocyte cells may be, or include, MPP5 and one or more of: thrombospondin type 1 domain containing (THSD)7A, protein tyrosine phosphatase receptor typo O (PTPRO), tubulin polymerization promoting protein (TPPP)3, lim homeobox transcription factor 1 beta (LMX1B), and / or nephrin (NPHS1). Alternatively, the genes characteristic of podocyte cells may include, or consist of, THSD7A, PTPRO, MPP5, TPPP3, LMX1B, andNPHSl.

[0065] In the methods of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, where the percentages of renal cells of the enriched heterogeneous renal cell population that express genes characteristic of UB, CM and podocyte cells may be determined, the enriched heterogeneous renal cell population may have been prepared from non-fetal renal tissue. The non-fetal renal tissue may of a kidney or a piece of kidney tissue, e.g. a biopsy, from a subject. The subject, may be of any age, e.g., greater than 1 month of age.

[0066] It should be understood that if the percentage of cells expressing a certain marker or expressing genes characteristic of UB / CM / podocyte cells 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 the percentage of cells 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.

[0067] 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., UB / CM marker (WNT11, GREM1, ETV5, HOX11, NCAM1, RET, FGF8, FGF10, CITED1, EYA1, SIX2, OSR1 and / or GDNF), podocyte marker (THSD7A, PTPRI, MMP5, TPPP3, LIMX1B and / or NPHS1), podocyte- PEC marker (hesl or CD44) or added marker ((TGFJ32), may be by detection of the marker(s) in a nucleic acid, e.g., mRNA or miRNA, polypeptide, or both nucleic acid and polypeptide, form and may be by any suitable assay / 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 (ELISA). 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.

[0068] 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. These renal cell types, in the enriched heterogeneous renal cell population, may be capable of, and may express, markers expressed by UB, CM and podocyte cells.

[0069] 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 inwhich 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 firaction(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 a cytokeratin, e.g., CK8, CK18 and / or CK19, characteristic of, e.g., renal epithelial, renal tubular, renal tubular epithelial, or renal proximal and / or distal tubular cells.

[0070] 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%, or less than about 4%, or less than about 3% 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 to about 48 hours, about 6 to about 36 hours, about 6 to about 24 hours, about 12 to about 48 hours, about 12 to about 36 hours, about 12 to about 24 hours, or about 12 to about 18 hours.

[0071] 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 akidney 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 separation step. Once the enriched heterogeneous renal cell population has been isolated, it may be frozen and / or analyzed prior to use as a therapeutic.

[0072] 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 formulated as a hydrogel composition or as a liquid composition. The pharmaceutical composition may, or may not, include hyaluronic acid.

[0073] 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 temperature-sensitive 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 throughout the 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.

[0074] 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.

[0075] 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 ashaving a therapeutic potential, the enriched heterogeneous renal cell population, or a pharmaceutical composition including 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 farther include endocrine dysfanctions such as anemia, e.g., erythropoietin-deficiency, and mineral imbalance, e.g., Vitamin D deficiency.

[0076] 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.

[0077] 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, or percutaneously. The enriched heterogeneous renal cell population, or pharmaceutical composition including 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 including 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.

[0078] The enriched heterogeneous renal cell population, or pharmaceutical composition including 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.

[0079] 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.

[0080] In some embodiments, the enriched heterogeneous renal cell population, which may or may not have been identified as having therapeutic potential, may be cultured in a 3- dimensional (D) system until it forms an organoid, e.g., a cluster of cells. The 3D culture system may be a suspension culture. In instances where the 3D culture system is a suspension culture, it may include a stirrer and lack a scaffold to which cells of the enriched heterogeneous renal cell population attach. The cells of the enriched heterogeneous renal cell population may be cultured in the 3D culture system from about 7 days to about 18 days to form the organoid. The cells of the enriched heterogeneous renal cell population may be cultured in the 3D culture system for about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, about 14 days, about 15 days, about 16 days, about 17 days, or about 18 days to form the organoid. An organoid, formed in the 3D culture system, may have a diameter of about 100 pm to about 800 pm. The organoid formed in the 3D culture system may have a diameter of about 100 pm to about 600 pm, or about 100 pm to about 400, or about 100 pm to about 200 pm, or about 200 pm to about 800 pm, or about 400 pm to about 800 pm, or about 600 pm to about 800 pm.

[0081] The organoid prepared from cells of the enriched heterogeneous renal cell population in the 3D culture system may have certain characteristics. Among these characteristics may be expression of certain markers, e.g., nucleic acid and protein markers. The certain markers that may be expressed by cells of the organoid may include any one or more (any one, any two, any three, any four, any five, any six, any seven or all eight) of Hoxal 1, CK8, Meis2, Thsd7a, Ptpro, CD13, LTL, and / or Cdc6. In some instances, the markers may be (i) Hoxal 1and Meis2, or (ii) Hoxal 1, Meis2 and CK8, or (iii) Thsd7a and Ptpro, or (iv) CD 13 and LTL, or (v) Cdc6, or (vi) Hoxal 1, Meis2, Thsd7a, and Ptpro, or (vii) Cdc6, Hoxal 1, Meis2, and Thsd7A, or (viii) Hoxal 1 and Thsd7A, or (ix) Cdc6, Hoxal 1 and Thsd7A, or (x) Ptpro, or (xi) Meis2, or (xii) Thsd7A. The organoid prepared from cells of the enriched heterogeneous renal cell population may also, or alternatively, exhibit certain structural characteristics. The certain structural characteristics exhibited may include nephron-like structures, e.g., structures having tubular-like and / or glomerulus-like features. In some instances, cells of the organoid may form structures that exhibit a glomerulus-like appearance. The structures that exhibit the glomerulus-like appearance may include structures having a PEC-like rim. Such structural characteristics may be exhibited by the organoid after or at about 6 to about 10 days, e.g., about 6 or about 7 or about 8 or about 9 or about 10 days, in culture. In some other instances, cells of the organoid may form structures that exhibit glomerular tuft like features. Such structural characteristics may be exhibited by the organoid at or after about 15 to 18 days, e.g., about 15 days or about 16 days or about 17 days or about 18 days, in culture. Further, cells of the organoid may form structures that exhibit tubular features. Such structural characteristics may be exhibited by the organoid at or after about 12 to about 18 days in culture, e.g., about 12 days, about 13 days, about 14 days, about 15 days, about 16 days, about 17 days, or about 18 days in culture.

[0082] The organoids prepared from the enriched heterogeneous renal cell population may be identified as having therapeutic potential if they express any marker, or exhibit any structural characteristic, as disclosed herein. By way of example, an organoid prepared from the enriched heterogeneous renal cell population may be identified as having therapeutic potential if expression of any one or more (e.g., any one, any two, any three, any four, any five, any six, any seven, or all eight) of Hoxal 1, CK8, Meis2, Thsd7a, Ptpro, CD13, LTL, and / or Cdc6 is detected. In some instances, the organoid prepared from the enriched heterogeneous renal cell population may be identified as having therapeutic potential if (i) Hoxal 1 and Meis2, or (ii) Hoxal 1, Meis2 and CK8, or (iii) Thsd7a and Ptpro, or (iv) CD 13 and LTL, or (v) Cdc6, or (vi) Hoxal 1, Meis2, Thsd7a, and Ptpro, or (vii) Cdc6, Hoxal 1, Meis2, and Thsd7A, or (viii) Hoxal 1 and Thsd7A, or (ix) Cdc6, Hoxal 1 and Thsd7A, or (x) Ptpro, or (xi) Meis2, or (xii) Thsd7A, is detected. The expression of the markers may be detected as described herein.

[0083] Further, the organoids prepared from the enriched heterogeneous renal cell population may be included in pharmaceutical compositions, may be administered to a patient in amethod of treating kidney disease, or may be for use in a method of treating kidney disease as described supra.

[0084] 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.

[0085] 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 - SRC population cells express markers associated with kidney development

[0086] Introduction'. An overarching hypothesis as to the mechanism by which human SRCs, an example enriched heterogeneous renal cell population, can repair and restore function to kidneys of kidney disease patients is that the SRCs may recapitulate aspects of fetal kidney development. In the developing kidney, signals from the UB trigger condensation of the metanephric mesenchyme to form a cap of renal precursor cells (Plisov SY, et al., Development. 2001; 725:1045-57). The CM undergoes mesenchymal-to-epithelial transition to form pretubular aggregates and renal vesicles which develop sequentially into comma- and S-shaped bodies and the epithelialized filtration apparatus (McMahon A., Curr Top Dev Biol. 2016;777:31-64; Thiagarajan RD, et al., PLoS One. 2011; 6:el7286, Plisov SY, et al., Development. 2001; 725:1045-57). Single cell transcriptomic analysis was performed to determine whether SRCs express UB, CM and podocyte markers.

[0087] Methods - Preparation of human SRCs. SRCs were isolated from biopsying human kidneys obtained from the National Disease Research Interchange (Philadelphia, PA; protocol# RRON2 01 001 A) or from kidney biopsies obtained from patients having type 2 diabetes (T2D) and chronic kidney disease (CKD) in a phase 2 clinical trial (NCT02836574) using a previously published method (Presnell SC, et al., Tissue Eng Part C Methods 2011; 77:261-73). Core renal biopsies (0.02 g) were collected with an EasyCore™ Biopsy System (Boston Scientific, Marlborough, MA), washed twice in Hanks balanced salt solution, minced, and digested for 30 min in dispase (Stem Cell Technologies, Canada) containing 300 U of collagenase type IV (Worthington Biochemical Corporation, Lakewood, NJ) and 5 mM CaCh (Sigma-Aldrich, St. Louis, MO). Source biopsy cells were cultured in 35 mm tissue culture dishes (Coming / Costar, Coming, NY) with viability determined by counting viable cells at passage and growth rates calculated as ln(fold increase) / time. Population doubling times were calculated as ln(2) / growth rate. Two milliliter suspensions of 60-75 million cells were loaded onto a density gradient (OptiPrep™ (STEMCELL TECHNOLOGIES, Cambridge, MA) in unsupplemented Keratinocyte Serum Free Media; Invitrogen, Waltham, MA), centrifuged at 800 g (sans brake) for 20 min at room temperature. The bottommost band was harvested with a pipette, washed twice in in sterile phosphate-buffered saline (PBS, Sigma-Aldrich), and resuspended in Dulbecco’s PBS (Sigma-Aldrich).

[0088] Methods - UB, CM and podocyte markers. An initial set of markers for UB, CM and podocyte was generated from publicly available renal atlases including The Human Fetal Kidney Atlas (The Human Fetal Kidney Atlas; Human fetal Kidney Atlas - Semraulab (leidenuniv.nl); last accessed 8 / 2 / 2023) and The Embryonic Development, Regenerative Medicine and Stem Cell Database (The Embryonic Development, Regenerative Medicine and Stem Cell Database; Embryonic Development Database - LifeMap Discovery (lifemapsc . com); last accessed 8 / 2 / 2023) and The Human BioMolecular Atlas Program (The Human BioMolecular Atlas Program; HuBMAP Consortium - The HuBMAP Human BioMolecular Atlas Program; last accessed 8 / 2 / 23). A refined list of anchor or canonical markers was then generated by verifying locoregional expression of a particular marker using the fetal kidney dataset from The Kidney Cell Atlas (The Kidney Cell Atlas; kidneycellatlas . org; last accessed 8 / 2 / 23).

[0089] Methods - Single Cell Transcriptomic Studies. Single cell RNA-seq was conducted by the Advanced Analytics Core at University of North Carolina at Chapel Hill (UNC, Chapel Hill, NC). Aliquots of SRCs (~lxl06cells in Dulbecco’s PBS, n=3 donors) were stained with acridine orange and propidium iodide and assessed for viability, concentration, and singleness using the LUNA-FX7 Dual Fluorescence Cell Counter (Logos Biosystems, South Korea). Cells were then processed using the lOx Genomics Chromium Controller (Pleasanton, CA) and their Chromium Single Cell 3' GEM, Library & Gel Bead Kit v3.1 Dual Index Kit (PN-1000268) following the manufacturer’s instructions. 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 Cl 000 thermal cycler (Bio-Rad, Hercules, CA) to generate complementary DNA (cDNA) libraries tagged with a cell barcode and unique molecular index (UMI). GEMs were then broken and purified using Dynabeads My One SILANE beads (Invitrogen, Waltham, MA) prior to 12 cDNA amplification cycles. Amplified cDNA libraries were purified with SPRIselect magnetic beads (Beckman Coulter, Brea, CA) and quantified using an Agilent Bioanalyzer High Sensitivity DNA chip (Agilent Technologies, Santa Clara, CA). 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 during 12 amplification cycles. Thecompleted sequencing libraries were then purified using SPRIselect beads, visualized using the Bioanalyzer High Sensitivity DNA chip (Agilent), and pooled in an equimolar ratio. Pooled libraries were sequenced on a NextSeq 2000 machine (Illumina, San Diego, CA) 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 with 7.1.0 with default settings. Analyses were made using 10X Genomics’ Loupe Browser (Tables 1 and 2) or Seurat (Seurat, v5.01; Tables 4 and 5).

[0090] Results - Rigorous mapping across various publicly available fetal kidney atlases was used to identify canonical, even anchor, markers for the UB, CM and podocytes. SRCs prepared from kidneys procured from NDRI were initially analyzed for expression of markers relatively specific to these UB, CM and podocyte precursor populations. Genes ret, wntll,are highly specific to the UB and CM and are expressed by these SRCs (Table 1). Genes thsd7a,ptpro, mpp5, tppp3, Imxlb, nphsl, and nphs2 are specific to podocytes and are expressed by these SRCs (Table 2).TABLE 1 : CM+UB Markers Expressed by SRC Population CellsTABLE 2: Podocyte Markers Expressed by SRC Population Cells

[0091] Using these markers, it was determined that approximately 21.17-38.52% of SRC population cells exhibited UB- / CM-specific gene expression with approximately 54.92-60.96 % of SRC population cells expressing podocyte markers. Table 3.TABLE 3: SRC Population Cells Expressing CM+UB-Specific or Podocyte-SpecificMarkers

[0092] Additional SRC UB, CM and podocyte expression analyses were performed to confirm this initial study. The additional analyses were conducted using SRCs that had been prepared from kidney biopsies of patients having type 2 diabetes and chronic kidney disease, and who were enrolled in a phase 2 clinical trial (NCT02836574) to investigate SRCs as a potential cell therapeutic. Table 4 provides scRNAseq expression data for UB+CM marker expression by these SRCs. Table 5 provides scRNAseq expression data for podocyte marker expression for these SRCs.TABLE 4: Percent SRC Population Cells Expressing CM+UB MarkersTABLE 5: Percent SRC Population Cells Expressing Podocyte Markers

[0093] The expression of these markers by SRCs is consistent with the expression of markers expressed by cells (UB, CM, and podocytes) involved in fetal kidney development. This gene expression data provides a mechanistic insight into SRCs' reparative and restorative activity in rodent models and stabilization of renal filtration in kidney disease subjects in clinical trials (Stavas J, et al., KI Reports 2022; 7:1619-1629; Stavas J, et al., Blood Purif. 2023; 52:114-121).EXAMPLE 2 - Organoids formed from SRC population cells express protein markers consistent with those expressed by cells in the developing kidney and acquire glomerular epithelial and tubular features

[0094] Introduction'. To gain further insight into SRCs mechanism of action, SRC-derived organoids were formed in a 3 -dimensional (3D) culture system. Proteins expressed, and structures formed, by the organoids were investigated to confirm Example 1 ’s SRCs gene expression data and determine SRCs ability to form nephron-like structures in a 3D culture environment.

[0095] Methods - Organoid formation. Human SRCs were prepared as described in Example 1. Organoids were formed from the SRCs by culture in renal cell growth medium (IxlO6cells / mL) in a spinner flask bioreactor (Coming, 3152) using a multimag stirrer (Genie; 80 rpm) up to 18 days at 37°C / 5% CO2.

[0096] Methods - Organoid characterization, size. Organoid diameters were measured using an EVOS M5000 Imaging System (Thermo Fisher, AMF5000).

[0097] Methods - Organoid characterization, markers. Organoid protein expression was determined by fixation (4% paraformaldehyde) and blocking, followed by staining with 3 Hg / mL immunofluorescent antibodies specific for characterization markers (Table 6) and matched isotype controls overnight at 4°C. Matched secondary antibodies plus Hoechst33342 nuclear dye were added at 1 gg / mL for 30 min, room temperature, using similar methods. Image analysis was performed using Celleste analysis software (Thermo Fisher).TABLE 6: Organoid characterization antibodies

[0098] Methods - Organoid characterization, structures. Organoids cultured up to 17 days were sectioned and stained with periodic acid Schiff (PAS).

[0099] Results -Organoids derived from human SRCs exhibited exponential growth over an 18-day culture period in 3D culture. FIG. 1.

[0100] Characterization of the human SRC-derived organoids by immunofluorescent antibody staining confirmed they expressed markers (Hoxal 1 (FIG. 2B), cytokeratin 8 (FIG. 2C) and Meis2 (FIG. 2D)) consistent with those expressed by ureteric bud+cap mesenchyme cells. It also detected expression of markers expressed by cells of the glomerular epithelium (Thds7a (FIG. 3 A) and Ptpro (FIG. 3B)), expressed by proximal tubule cells (LTL (FIG. 4A) and CD13 (FIG. 4A and 4B)), and cell division cycling protein Cdc6 (FIG. 5B).

[0101] Moreover, sectioning of SRC-derived organoids revealed the presence of morphologic features consistent with glomerular-like and tubular structures. Sectioned 8-day cultured SRC-derived organoids exhibited structures having a glomerulus-like appearance including a PEC-like rim (FIG. 6A, arrow). In sectioned SRC-derived organoids cultured 17 days, the organoids exhibited nephron-like features including glomerular tuft-like structures (FIG. 6B, arrows) and tubular structures (FIG. 7A-7B).

[0102] Overall, 3D cultured human SRC-derived organoids’ expression of markers characteristic of ureteric bud + cap mesenchyme, glomerular epithelial and proximal tubular cells, and acquisition of glomerular epithelial and tubular structural features demonstrates apotential reparative capacity underlying SRCs therapeutic effects in animal models of CKD and stabilization of eGFR in patients with type 2 diabetes and CKD in clinical trials.EXAMPLE 3 - Osteopontin-mediated reparative effects of selected renal cells

[0103] Introduction'. Osteopontin (OPN) conveys renal reparative effects. To further investigate mechanisms by which SRCs exhibit reparative and restorative effects in models of CKD, an investigation was performed to determine whether OPN is involved in, or mediates, SRC reparative activity.

[0104] Methods'. Human SRC (National Disease Research Interchange) and renal cortical biopsy (control) monolayers were submitted to a scratch assay in the absence / presence of an OPN neutralizing antibody. Reparative activity was evaluated by imaging (blinded) the number of cells migrating to bridge the wound. Expression of cavl, mmp9, icaml and cxcr4 was evaluated using qPCR. Genes were seeded into HumanBase for visualization of transcriptome fimction.

[0105] Results'. Compared to control, SRCs exhibited increased migration into the wound (p<0.05), an effect reduced by an OPN antibody (p<0.05). Expression of migratory markers cavl, mmp9, icaml and cxcr4 were upregulated in SRCs (p<0.05). Both these findings are consistent with those reported in WO 2011 / 143499, incorporated herein by reference for all purposes. Further investigation, using Gene ontology, confirmed that the opn / sspl-cavl- mmp9-icaml-cxcr4 axis regulates migration, adhesion, and wound healing in the kidney. See FIG. 8.

[0106] These data suggest that SRC reparative effects, e.g., preservation of renal microarchitecture and maintenance of the renal filtration function, including creatinine clearance, electrolyte balance, fluid homeostasis, urine concentration and Cystatin C metabolism, may be mediated, in part, by an OPN-associated cascade.EXAMPLE 4 - SRCs share a podocyte-parietal epithelial cell transcriptome

[0107] Introduction'. Among effects associated with SRC administration are improved glomerular barrier function, renal filtration, and preservation of renal microarchitecture and glomerular integrity. As a mechanism of these beneficial effects, it was investigated as to whether SRCs share a podocyte-parietal epithelial cell (PEC) transcriptome, associated with renal repair and restoration.

[0108] Methods'. The intersection set of podocyte-PEC genes and directionally aligned SRC genes were seeded into miRNet and Cytoscape for visualization of the shared transcriptomeand identification of its functional attributes. Human SRCs (National Disease Research Interchange kidneys) were submitted to scRNA-seq, as described in Example 1, to map gene expression.

[0109] Results', osrl, six2, lhxl,fgf8, Ifng, nphsl, nphs2, vegfa, cd44 and hesl are expressed by both podocyte-PEC and SRCs and involved in kidney developmental functions including maintenance of undifferentiated nephron precursors, tube and nephron formation, maturation of the glomerular barrier and formation of the glomerular capillary bed. See Table 7 and FIG.9. VEGFA emerged as the hub gene within this network (FIG. 10).TABLE 7: Podocyte-PEC genes expressed by SRC population cells

[0110] Hesl, a gene associated with nephron development, in particular, was found to be expressed by about 79% to about 89% of SRCs. See Table 8 and FIG. 11.TABLE 8: hesl expression by SRCs

[0111] A VEGF-A anchored podocyte-PEC transcriptome expressed by SRCs may recapitulate events associated with kidney development and mediate the improved glomerular integrity, renal microarchitecture and renal filtration observed in CKD models.

[0112] 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: (i) ureteric bud and / or cap mesenchyme (UB / CM) marker; and / or (ii) podocyte marker, wherein the at least one UB / CM marker comprises one or more of: Wingless -related integration site family member 11 (WNT11), Gremlin (GREM)l, E26 transformation-specific (ETS) variant transcription 5 (ETV5), Homeobox (HOX)ll and neural cell adhesion molecule (NCAM)l, wherein the at least one podocyte marker comprises one or more of: thrombospondin type 1 domain containing (THSD)7A, protein tyrosine phosphatase receptor type O (PTPRO), matrix metalloproteinase (MPP)5, tubulin polymerization promoting protein (TPPP)3, lim homeobox transcription factor 1 beta (LMX1B); 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: (i) UB / CM marker and / or (ii) podocyte marker.

2. The method of claim 1, wherein the step of determining comprises determining whether cells of the enriched heterogeneous renal cell population express the at least one (i) UB / CM marker, and wherein 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 (i) UB / CM marker.

3. The method of claim 2, wherein the step of determining comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one (i) UB / CM marker.

4. The method of claim 2, wherein the at least one (i) UB / CM marker comprises WNT11.

5. The method of claim 3, wherein the at least one (i) UB / CM marker comprises WNT11, 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 1 % of cells of the enriched heterogeneous renal cell population express WNT11.

6. The method of claim 2, wherein the at least one (i) UB / CM marker comprises GREM1.

7. The method of claim 3, wherein the at least one (i) UB / CM marker comprises GREM1 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 5% of cells of the enriched heterogeneous renal cell population express GREM1.

8. The method of claim 3, wherein the at least one (i) UB / CM marker comprises GREM1 and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1.

9. The method of claim 2, wherein the at least one (i) UB / CM marker comprises ETV5.

10. The method of claim 3, wherein the at least one (i) UB / CM marker comprises ETV5 and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5.

11. The method of claim 3, wherein the at least one (i) UB / CM marker comprises ETV5 and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5.

12. The method of claim 2, wherein the at least one (i) UB / CM marker comprises HOX11.

13. The method of claim 3, wherein the at least one (i) UB / CM marker comprises HOX11 and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11.

14. The method of claim 3, wherein the at least one (i) UB / CM marker comprises HOX11 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 HOX11.

15. The method of claim 2, wherein the at least one (i) UB / CM marker comprises NCAM1.

16. The method of claim 3, wherein the at least one (i) UB / CM marker comprises NCAM1 and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1.

17. The method of claim 3, wherein the at least one (i) UB / CM marker comprises NCAM1 and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1 % and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1.

18. The method of claim 2, wherein the at least one (i) UB / CM marker comprises:(a) WNT11 and GREMl;(b) WNT11 and ETV5;(c) WNT11 and HOXll;(d) WNT11 and NCAMl;(e) GREM1 and ETV5;(f) GREM1 and HOXll;(g) GREM1 andNCAMl;(h) ETV5 and HOXll;(i) ETV5 and NCAMl; or(j) HOX11 andNCAMl.

19. The method of claim 3, wherein the at least one (i) UB / CM marker comprises:(a) WNT11 and GREMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, and greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1;(b) WNT11 and ETV5, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, and greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5;(c) WNT11 and HOXll, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11 and greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11;(d) WNT11 and NCAMl; 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(e) GREM1 and ETV5, 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 5% of cells of the enriched heterogeneous renal cell population express GREM1, and greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5;(f) GREM1 and HOXll, 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 5% of cells of the enriched heterogeneous renal cell population express GREM1 and greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11;(g) GREM1 andNCAMl, 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 5% of cells of the enriched heterogeneous renal cell population express GREM1, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(h) ETV5 and HOXll, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11;(i) ETV5 and NCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1; or(j) HOX11 andNCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population expressHOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1.

20. The method of claim 3, wherein the at least one (i) UB / CM marker comprises:(a) WNT11 and GREMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, and greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1;(b) WNT11 and ETV5, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, and greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5;(c) WNT11 and HOXll, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11;(d) WNT11 and NCAMl; 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(e) GREM1 and ETV5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most aboutand greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5;(f) GREM1 and HOXll, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11;(g) GREM1 andNCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(h) ETV5 and HOXll, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11;(i) ETV5 and NCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1; or(j) HOX11 andNCAMl, 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 HOX11, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1.

21. The method of claim 2, wherein the at least one (i) UB / CM marker comprises:(a) WNTllj GREMl and ETV5;(b) WNT11, GREM1 and HOXll;(c) WNTllj GREMl and NCAMl;(d) WNT11 , ETV5 and HOX11 ;(e) WNT11, ETV5 andNCAMl;(f) WNT11, HOX11 and NCAMl;(g) GREM1, ETV5 and HOXll;(h) GREM1, ETV5 andNCAMl;(i) GREM1, HOX11 and NCAMl; or(j) ETV, HOX11 and NCAMl.

22. The method of claim 3, wherein the at least one (i) UB / CM marker comprises:(a) WNT11, GREM1 and ETV5, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1, and greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5;(b) WNT11, GREM1 and HOXll, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1 and greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11 ;(c) WNT11, GREM1 and NCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1, and greater than about .25% and at most about2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(d) WNT11, ETV5 and HOX11, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11 ;(e) WNT11, ETV5 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(f) WNT11, HOX11 and NCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(g) GREM1, ETV5 and HOXll, 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 5% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 2% andat most about 20% of cells of the enriched heterogeneous renal cell population express HOX11 ;(h) GREM1, ETV5 andNCAMl, 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 5% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(i) GREM1, HOX11 andNCAMl, 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 5% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1; or(j) ETV5, HOX11 andNCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1.

23. The method of claim 3, wherein the at least one (i) UB / CM marker comprises:(a) WNT11, GREM1 and ETV5, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 5% and at most about 35% of cells of the enriched heterogeneousrenal cell population express GREM1, and greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5;(b) WNT11, GREM1 and HOXll, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11;(c) WNT11, GREM1 and NCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(d) WNT11, ETV5 and HOXll, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11 ;(e) WNT11, ETV5 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about 1% andat most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(f) WNT11, HOX11 and NCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(g) GREM1, ETV5 and HOXll, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11 ;(h) GREM1, ETV5 andNCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(i) GREM1, HOX11 and NCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about 1%and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1; or(j) ETV5, HOX11 andNCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about 1 % and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1.

24. The method of claim 2, wherein the at least one (i) UB / CM marker comprises:(a) WNT11 , GREM1 , ETV5 and HOX11 ;(b) WNT11, GREM1, ETV5 andNCAMl;(c) WNT11, ETV5, HOX11 andNCAMl;(d) WNT11, GREM1, HOX11 andNCAMl; or(e) GREM1, ETV5, HOX11 and NCAMl.

25. The method of claim 3, wherein the at least one (i) UB / CM marker comprises:(a) WNT11, GREM1, ETV5 and HOXll, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11;(b) WNT11, GREM1, ETV5 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 0% and at most about 5% of cells of the enriched heterogeneous renalcell population express GREM1, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(c) WNT11, ETV5, HOX11 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1;(d) WNT11, GREM1, HOX11 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1; or(e) GREM1, ETV5, HOX11 and NCAMl, 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 5% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1.

6. The method of claim 3, wherein the at least one (i) UB / CM marker comprises:(a) WNT11, GREM1, ETV5 and HOXll, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5 and greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11;(b) WNT11, GREM1, ETV5 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(c) WNT11, ETV5, HOX11 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1;(d) WNT11, GREM1, HOX11 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 5% and at most about 35% of cells of the enriched heterogeneousrenal cell population express GREM1, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1; or(e) GREM1, ETV5, HOX11 andNCAMl, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1.

27. The method of claim 2, wherein the at least one (i) UB / CM marker comprises: WNT11, GREM1, ETV5, HOX11 andNCAMl.

28. The method of claim 3, wherein the at least one (i) UB / CM marker comprises: WNT11, GREM1, ETV5, HOX11 andNCAMl, 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 1% of cells of the enriched heterogeneous renal cell population express WNT11, greater than 0% and at most about 5% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 2% and at most about 25% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 2% and at most about 20% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about .25% and at most about 2.5% of cells of the enriched heterogeneous renal cell population express NCAM1.

29. The method of claim 3, wherein the at least one (i) UB / CM marker comprises: WNT11, GREM1, ETV5, HOX11 andNCAMl, 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 1% ofcells of the enriched heterogeneous renal cell population express WNT11, greater than 5% and at most about 35% of cells of the enriched heterogeneous renal cell population express GREM1, greater than about 50% and at most about 70% of cells of the enriched heterogeneous renal cell population express ETV5, greater than about 15% and at most about 30% of cells of the enriched heterogeneous renal cell population express HOX11, and greater than about 1% and at most about 7% of cells of the enriched heterogeneous renal cell population express NCAM1.

30. The method of claim 1, wherein the step of determining comprises determining whether cells of cells of the enriched heterogeneous renal cell population express the at least one (ii) podocyte marker, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if cells of the enriched heterogeneous renal cell population are determined to express the at least one (ii) podocyte marker.

31. The method of any of claims 2-30, wherein the step of determining further comprises determining whether cells of the enriched heterogeneous renal cell population express the at least one (ii) podocyte marker, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if cells of the enriched heterogeneous renal cell population are fiirther determined to express the at least one (ii) podocyte marker.

32. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises THSD7A.

33. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises PTPRO.

34. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises MPP5.

35. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises TPPP3.

36. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises LMX1B.

37. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A and PTPRO;(b) THSD7A and MPP5;(c) THSD7A and TPPP3;(d) THSD7A and LMX1B;(e) PTPRO and MPP5;(f) PTPRO and TPPP3;(g) PTPRO and LMX1B;(h) MPP5 and TPPP3;(i) MPP5 and LMX1B; or(j) TPPP3 and LMX1B.

38. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A, PTPRO and MPP5;(b) THSD7A, PTPRO and TPPP3;(c) THSD7A, PTPRO and LMX1B;(d) THSD7A, MPP5 and TPPP3;(e) THSD7A, MPP5 and LMX1B;(f) THSD7A, TPPP3 and LMX1B;(g) PTPRO, MPP5 and TPPP3;(h) PTPRO, MPP5 and LMX1B;(i) PTPRO, TPPP3 and LMX1B; or(j) MPP5, TPPP3 and LMX1B.

39. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A, PTPRO, MPP5 and TPPP3;(b) THSD7A, PTPRO, MPP5 and LMX1B;(c) THSD7A, MPP5, TPPP3 and LMX1B;(d) THSD7A, PTPRO, TPPP3 and LMX1B; or(e) GREM1, MPP5, TPPP3 and LMX1B.

40. The method of claim 30 or 31, wherein the at least one (ii) podocyte marker comprises THSD7A, PTPRO, MPP5, TPPP3, and LMX1B.

41. The method of claim 30 or 31 , wherein the step of determining comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one (ii) podocyte marker.

42. The method of claim 41, wherein the at least one (ii) podocyte marker comprises THSD7A, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A.

43. The method of claim 41, wherein the at least one (ii) podocyte marker comprises THSD7A, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A.

44. The method of claim 41, wherein the at least one (ii) podocyte marker comprises PTPRO, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO.

45. The method of claim 41, wherein the at least one (ii) podocyte marker comprisesPTPRO, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO.

46. The method of claim 41, wherein the at least one (ii) podocyte marker comprises MPP5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5.

47. The method of claim 41, wherein the at least one (ii) podocyte marker comprises MPP5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5.

48. The method of claim 41, wherein the at least one (ii) podocyte marker comprises TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3.

49. The method of claim 41, wherein the at least one (ii) podocyte marker comprises LMX1B, 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 .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

50. The method of claim 41, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A and PTPRO, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, and greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO;(b) THSD7A and MPP5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, and greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5;(c) THSD7A and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(d) THSD7A and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(e) PTPRO and MPP5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5;(f) PTPRO and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population expressPTPRO, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(g) PTPRO and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(h) MPP5 and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(i) MPP5 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B; or(j) TPPP3 and LMXlB, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

51. The method of claim 41, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A and PTPRO, 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 30% of cells of the enriched heterogeneous renal cell population expressTHSD7A, and greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO;(b) THSD7A and MPP5, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, and greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5;(c) THSD7A and TPPP3, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(d) THSD7A and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(e) PTPRO and MPP5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5;(f) PTPRO and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(g) PTPRO and LMX1B, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(h) MPP5 and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(i) MPP5 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B; or(j) TPPP3 and LMXlB, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

52. The method of claim 41, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A, PTPRO and MPP5, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5;(b) THSD7A, PTPRO and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(c) THSD7A, PTPRO and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(d) THSD7A, MPP5 and TPPP3; and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(e) THSD7A, MPP5 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(f) THSD7A, TPPP3 and LMX1B, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(g) PTPRO, MPP5 and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(h) PTPRO, MPP5 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(i) PTPRO, TPPP3 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B; or(j) MPP5, TPPP3 and LMX1B, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

53. The method of claim 41, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A, PTPRO and MPP5, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 2.5 % and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5;(b) THSD7A, PTPRO and TPPP3, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(c) THSD7A, PTPRO and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(d) THSD7A, MPP5 and TPPP3; 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(e) THSD7A, MPP5 and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(f) THSD7A, TPPP3 and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(g) PTPRO, MPP5 and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(h) PTPRO, MPP5 and LMX1B, andwherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(i) PTPRO, TPPP3 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B; or(j) MPP5, TPPP3 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

54. The method of claim 41, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A, PTPRO, MPP5 and TPPP3, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell populationexpress MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(b) THSD7A, PTPRO, MPP5 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(c) THSD7A, MPP5, TPPP3 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(d) THSD7A, PTPRO, TPPP3 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B; or(e) PTPRO, MPP5, TPPP3 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population expressPTPRO, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

55. The method of claim 41, wherein the at least one (ii) podocyte marker comprises:(a) THSD7A, PTPRO, MPP5 and TPPP3, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3;(b) THSD7A, PTPRO, MPP5 and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(c) THSD7A, MPP5, TPPP3 and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell populationexpress TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B;(d) THSD7A, PTPRO, TPPP3 and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B; or(e) PTPRO, MPP5, TPPP3 and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

56. The method of claim 41, wherein the at least one (ii) podocyte marker comprises THSD7A, PTPRO, MPP5, TPPP3, and LMX1B, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 1.5% and at most about 6% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about .1% and at most about 3% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 40% and at most about 70% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

57. The method of claim 41, wherein the at least one (ii) podocyte marker comprises THSD7A, PTPRO, MPP5, TPPP3, and LMX1B, 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 30% of cells of the enriched heterogeneous renal cell population express THSD7A, greater than about 2.5% and at most about 10% of cells of the enriched heterogeneous renal cell population express PTPRO, greater than about 80% and at most about 95% of cells of the enriched heterogeneous renal cell population express MPP5, greater than about .1% and at most about .6% of cells of the enriched heterogeneous renal cell population express TPPP3, and greater than 0% and at most about .4% of cells of the enriched heterogeneous renal cell population express LMX1B.

58. The method of any preceding claim, fiirther comprising detecting at least one further marker, wherein the at least one further marker is a further UB / CM marker, wherein the at least one further marker comprises one or more of: rearranged during transfection (RET), fibroblast growth factor (FGF)8, FGF10, cbp / P300 interacting transactivator (CITED) 1, eyes absent (EYA)l, sine oculis homeobox homolog 2 (SIX2), odd-skipped related 1 (OSR1) and / or glial cell derived neurotrophic factor (GDNF), and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if cells of the enriched heterogeneous renal cell population are further determined to express the at least one further marker.

59. The method of any preceding claim, wherein the step of determining further comprises determining whether cells of the enriched heterogeneous renal cell population express at least one podocyte-PEC marker, and wherein the enriched heterogeneous renal cell population is identified as having therapeutic potential if cells of the enriched heterogeneous renal cell population are further determined to express the at least one podocyte-PEC marker wherein the at least one podocyte-PEC marker comprises hesl.

60. The method of claim 59, wherein the determining whether cells of the enriched heterogeneous renal cell population express the at least one podocyte-PEC marker comprises determining percentage of cells of the enriched heterogeneous renal cell population that express the at least one podocyte-PEC marker.

61. The method of claim 60, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 70% of cells of the enriched heterogeneous renal cell population express hesl.

62. The method of any preceding claim, fiirther comprising: determining whether cells of the enriched heterogeneous renal cell population express transforming growth factor beta 2 (TGF02), 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 TGF02.

63. The method of claim 62, wherein the determining comprises determining percentage of cells of the enriched heterogeneous renal cell population that express TGF02, and wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that greater than about 50% of cells of the enriched heterogeneous renal cell population express TGF02.

64. The method of claim 62, wherein the determining comprises determining whether cells of the enriched heterogeneous renal cell population secrete TGF02.

65. The method of claim 64, wherein the determining whether cells of the enriched heterogeneous renal cell population secrete TGFP2 further comprises determining amount TGFp2 secreted by the cells, wherein the enriched heterogeneous renal cell population is identified as having a therapeutic potential if it is determined that at least about 1.0 ng TGF02 is secreted per 1,000,000 enriched heterogeneous renal cell population cells.

66. A method of identifying an enriched heterogeneous renal cell population as having a therapeutic potential, comprising: determining percentages of renal cells of the population expressing genes characteristic of ureteric bud (UB), cap mesenchyme (CM) and podocyte cells; and identifying the population as having a therapeutic potential if it is determined that:(i) between about 20% and about 40% of renal cells of the population express genes characteristic of UB and CM cells; and(ii) between about 50% and about 65% of renal cells of the population express genes characteristic of podocyte cells; wherein the population is prepared from non-fetal renal tissue.

67. The method of claim 66, wherein the genes characteristic of the UB and CM cells comprise: Wingless-related integration site family member 11 (WNT11), Gremlin (GREM)l, E26 transformation-specific (ETS) variant transcription 5 (ETV5), Homeobox (HOX)ll, neural cell adhesion molecule (NCAM)l, rearranged during transfection (RET), fibroblast growth factor 8 (FGF8), FGF10, cbp / P300 interacting transactivator (CITED)l, eyes absent (EYA)l, sine oculis homeobox homolog 2 (SIX2), odd-skipped related 1 (OSR1) and glial cell derived neurotrophic factor (GDNF).

68. The method of claim 66, wherein the genes characteristic of the podocyte cells comprise matrix metalloproteinase (MPP)5.

69. The method of claim 67, wherein the genes characteristic of the podocyte cells comprise matrix metalloproteinase (MPP)5.

70. The method of claim 68 or 69, wherein the genes characteristic of the podocyte cells further comprise thrombospondin type 1 domain containing (THSD)7A, protein tyrosine phosphatase receptor typo O (PTPRO), tubulin polymerization promoting protein (TPPP)3, lim homeobox transcription factor 1 beta (LMX1B), and nephrin (NPHS1).

71. The method of any of claims 66, 67, or 70, wherein the genes characteristic of the UB and CM cells consist of WNT11, GREM1, ETV5, HOX11, NCAM1, RET, FGF8, FGF10, CITED1, EYA1, SIX2, OSR1 and GDNF.

72. The method of any of claims 66, 67, or 70, wherein the genes characteristic of the podocyte cells consist of THSD7A, PTPRI, MMP5, TPPP3, LIMX1B andNPHSl.

73. An enriched heterogeneous renal cell population identified according to the method of any preceding claim.

74. A pharmaceutical composition comprising the enriched heterogeneous renal cell population of claim 73.

75. 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 74.

76. Use of the pharmaceutical composition of claim 74 in the manufacture of a medicament to treat kidney disease.

77. The enriched heterogeneous renal cell population of claim 73, wherein the population is prepared via a method comprising a step of centrifugation using a density medium.

78. The enriched heterogeneous renal cell population of claim 77, wherein the population comprises cells of a buoyant density greater than about 1.04 g / mL.

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