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Updated: May 10, 2026
Optimized Protocol for Generating Functional Pancreatic Insulin-secreting Cells from Human Pluripotent Stem Cells
Published on: February 2, 2024
Recent progress in generation of human surrogate β cells
1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University Ramat Aviv, Tel Aviv, Israel. sefrat@post.tau.ac.il
Purpose Of Review:
This review evaluates recent progress in several approaches aimed at developing human surrogate β cells, and identifies gaps that need to be filled for bringing them closer to clinical application.
Recent Findings:
Cells expanded in vitro from human cadaver donor β cells under conditions causing dedifferentiation have been shown to undergo redifferentiation following inhibition of the Notch pathway. Efforts for differentiation of insulin-producing cells from human pluripotent stem cells have focused on isolation and expansion of intermediate-stage cells. The role of mesenchyme in expansion of pancreas progenitors has been emphasized by mouse cell ablation, and co-culture of human embryonic stem cell-derived definitive endoderm with mesenchyme. Incomplete removal of Polycomb-mediated repression of endocrine genes in embryonic stem cell-derived insulin-producing cells generated in vitro has been suggested to be responsible for their immature phenotype. Induced pluripotent stem cells reprogrammed from β cells have been shown to exhibit an enhanced differentiation capacity toward insulin-producing cells, compared with other pluripotent stem cells. A new approach for reprogramming non-β into β-like cells involving transcription factor gene ablation has been demonstrated in mouse enteroendocrine cells in vivo.
Summary:
New insights into the stumbling blocks in expansion of human donor islet cells, differentiation of pluripotent stem cells, and reprogramming of non-β cell types are shaping improved strategies, which are likely to bring us closer to the goal of generating abundant human surrogate β cells.
Insights
Developing human surrogate beta cells is advancing through strategies like redifferentiation of donor cells and improved stem cell differentiation. These efforts aim to overcome challenges for clinical application.
Area of Science:
- * Regenerative Medicine
- * Stem Cell Biology
- * Diabetes Research
Background:
- * Current limitations in generating functional human beta cells for transplantation.
- * The need for scalable and safe sources of insulin-producing cells.
- * Understanding beta cell biology and developmental pathways is crucial.
Purpose of the Study:
- * To review recent advancements in developing human surrogate beta cells.
- * To identify key challenges hindering clinical translation.
- * To highlight strategies for overcoming these obstacles.
Main Methods:
- * Analysis of in vitro differentiation and reprogramming techniques.
- * Evaluation of stem cell-based approaches for beta cell generation.
- * Review of studies on donor beta cell expansion and redifferentiation.
Main Results:
- * Successful redifferentiation of dedifferentiated donor beta cells via Notch pathway inhibition.
- * Progress in isolating and expanding intermediate-stage cells from pluripotent stem cells.
- * Demonstrated role of mesenchyme in pancreas progenitor expansion.
- * Identified incomplete Polycomb-mediated repression as a cause of immature in vitro beta cell phenotype.
- * Induced pluripotent stem cells from beta cells show enhanced differentiation capacity.
- * In vivo reprogramming of non-beta cells into beta-like cells achieved in mice.
Conclusions:
- * New strategies are emerging based on insights into donor cell expansion, stem cell differentiation, and cell reprogramming.
- * Overcoming current roadblocks will facilitate the generation of abundant human surrogate beta cells.
- * These advancements bring the clinical application of beta cell replacement therapies closer.
