Human pancreatic beta-like cells converted from fibroblasts

Saiyong Zhu, Holger A. Russ, Xiaojing Wang, Mingliang Zhang, Tianhua Ma, Tao Xu, Shibing Tang, Matthias Hebrok () and Sheng Ding ()
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Saiyong Zhu: Gladstone Institute of Cardiovascular Disease, University of California
Holger A. Russ: Diabetes Center, University of California, San Francisco
Xiaojing Wang: Gladstone Institute of Cardiovascular Disease, University of California
Mingliang Zhang: Gladstone Institute of Cardiovascular Disease, University of California
Tianhua Ma: Gladstone Institute of Cardiovascular Disease, University of California
Tao Xu: Gladstone Institute of Cardiovascular Disease, University of California
Shibing Tang: Gladstone Institute of Cardiovascular Disease, University of California
Matthias Hebrok: Diabetes Center, University of California, San Francisco
Sheng Ding: Gladstone Institute of Cardiovascular Disease, University of California

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro. Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes.

Date: 2016
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DOI: 10.1038/ncomms10080

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