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Cell Stem Cell. 2014 Feb 6;14(2):228-36. doi: 10.1016/j.stem.2014.01.006.

Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages.

Author information

1
Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Diabetes Center, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
3
Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: sheng.ding@gladstone.ucsf.edu.

Abstract

Pancreatic β cells are of great interest for the treatment of type 1 diabetes. A number of strategies already exist for the generation of β cells, but a general approach for reprogramming nonendodermal cells into β cells could provide an attractive alternative in a variety of contexts. Here, we describe a stepwise method in which pluripotency reprogramming factors were transiently expressed in fibroblasts in conjunction with a unique combination of soluble molecules to generate definitive endoderm-like cells that did not pass through a pluripotent state. These endoderm-like cells were then directed toward pancreatic lineages using further combinations of small molecules in vitro. The resulting pancreatic progenitor-like cells could mature into cells of all three pancreatic lineages in vivo, including functional, insulin-secreting β-like cells that help to ameliorate hyperglycemia. Our findings may therefore provide a useful approach for generating large numbers of functional β cells for disease modeling and, ultimately, cell-based therapy.

PMID:
24506886
PMCID:
PMC4747235
DOI:
10.1016/j.stem.2014.01.006
[Indexed for MEDLINE]
Free PMC Article

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