In Vitro Differentiation and Expansion of Human Pluripotent Stem Cell-Derived Pancreatic Progenitors

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The Review of Diabetic Studies,2014,11,1,19-34.
Published:May 2014
Type:Review Article
Author(s) affiliations:

Jolanta Chmielowiec1,2,3,4 and Malgorzata Borowiak1,2,3,4

1Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

2Center for Cell and Gene Therapy, Baylor College of Medicine, TEXAS.

3Molecular and Cellular Biology Department, Baylor College of Medicine, TEXAS.

4McNair Medical Institute, Baylor College of Medicine, TEXAS.


Recent progress in understanding stem cell biology has been remarkable, especially in deciphering signals that support differentiation towards tissue-specific lineages. This achievement positions us firmly at the beginning of an era of patient-specific regenerative medicine and human disease modeling. It will be necessary to equip the progress in this era with a reliable source of self-renewing progenitor cells that differentiate into functional target cells. The generation of pancreatic progenitors that mature in vivo into functional beta-cells has raised the hope for new therapeutic options in diabetes, but key challenges still remain including the production of sufficient numbers of cells for research and transplantation. Recent approaches to this problem have shown that the presence of organ- and stage-specific mesenchyme improves the generation of progenitors, from endoderm to endocrine cells. Alternatively, utilization of threedimensional culture may improve the efficiency and yield of directed differentiation. Here, we review the current knowledge of pancreatic directed differentiation and ex vivo expansion of pancreatic progenitors, including recent advances in differentiation strategies for the generation of pancreatic progenitors, and we discuss persistent challenges which will need to be overcome before personalized cell-based therapy becomes a practical strategy.