Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells.
Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature beta cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet beta cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDX1-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insulin-producing cells. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.
Zhang
Donghui
D
Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, China.
Jiang
Wei
W
Liu
Meng
M
Sui
Xin
X
Yin
Xiaolei
X
Chen
Song
S
Shi
Yan
Y
Deng
Hongkui
H
D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000378:metabolism
D002096:C-Peptide; D018398:Homeodomain Proteins; C105201:NKX6-1 protein, human; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D004815:Epidermal Growth Factor