Stem Cell Beta-Like Cell Screening Using Novel Biomarkers
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Solution Overview
Problem
Current methods for identifying beta-like cells derived from pluripotent stem cells using classical markers are insufficient, as they fail to predict which cells will maintain insulin expression and secretion after transplantation, leading to suboptimal differentiation and potential selection of undesired cell populations.
Innovation Solution
The use of specific markers such as NKX6.1 in combination with ACVR1C, FREM2, CHRNA3, DCC, SOX11, MARCKSL1, BASP1, STARD10, AMBP, ST6GALNAC5, HMGCS1, ELAVL2, PCP4, PCDH7, NEFL, PLAGL1, EGFL7, RAD21, RTN1, PLXNA2, LBH, NEFM, SLC30A8, DLK1, and MAFB to identify beta-like cells that maintain insulin expression and secretion after transplantation, distinguishing them from native human beta cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If classical beta cell markers (INS, PDX1, NKX6.1) are used to identify stem cell derived beta like cells, then the cells appear phenotypically similar to native human beta cells in vitro, but they fail to maintain insulin expression and secretion after transplantation
Solution Approach 1:
The patent changes the identification parameters from classical markers (INS, PDX1, NKX6.1) to a new set of markers (ACVR1C, FREM2, CHRNA3, DCC, SOX11, MARCKSL1, BASP1, STARD10, AMBP, ST6GALNAC5, HMGCS1, ELAVL2, PCP4, PCDH7, NEFL, PLAGL1, EGFL7, RAD21, RTN1, PLXNA2, LBH, NEFM, SLC30A8, DLK1, MAFB, ISL1) that accurately predict post-transplantation functionality. This parameter change enables precise identification of cells that will maintain insulin secretion capability in vivo.
2Manufacturing precision
If differentiation protocols are optimized towards cells expressing classical beta cell markers, then the cell population resembles native human beta cells before transplantation, but the phenotype changes after transplantation leading to loss of function
Solution Approach 1:
The patent applies preliminary action by using the new marker panel to identify and select beta-like cells before transplantation that already possess the functional characteristics needed for post-transplantation survival. This preliminary identification ensures that only cells with stable phenotypic potential are selected, preventing phenotype change after transplantation.
3Reliability
If donor pancreatic islets are used for transplantation, then some patients achieve insulin independence, but donor islets are scarce and of variable quality
Solution Approach 1:
The patent creates a copy of functional beta cells by deriving them from pluripotent stem cells rather than using natural donor islets. The new marker system ensures these copied cells accurately replicate the functional properties of native beta cells, providing an unlimited source of high-quality transplantable cells with consistent efficacy.
Data Source
AI summary
The present invention relates to a method for screening for beta like cells in an in vitro cell population of pluripotent stem cell derived cells, wherein the method comprises a step of identifying the beta like cells expressing specific markers or combinations thereof for predicting the in vivo functionality of said cells prior to transplantation. The present invention also relates to an in vitro population of pluripotent stem cell derived beta like cells, wherein the beta like cell comprises one or more markers that is absent in native human beta cell or the expression level of said marker is different than in native human beta cells.