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Recent progress in generation of human surrogate β cells

Efrat, Shimon

Current Opinion in Endocrinology & Diabetes and Obesity: August 2013 - Volume 20 - Issue 4 - p 259–264
doi: 10.1097/MED.0b013e32836313d4
DIABETES AND THE ENDOCRINE PANCREAS II: Edited by Peter A. Gottlieb

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.

Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University Ramat Aviv, Tel Aviv, Israel

Correspondence to Shimon Efrat, Department of Human Molecular Genetics and Biochemistry Sackler School of Medicine, Tel Aviv University Ramat Aviv, Tel Aviv 69978, Israel. Tel: +972 3 640 7701; fax: +972 3 640 9950; e-mail: sefrat@post.tau.ac.il

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