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In vitro derivation of functional insulin-producing cells from human embryonic stem cells
Jiang, Wei ; Shi, Yan ; Zhao, Dongxin ; Chen, Song ; Yong, Jun ; Zhang, Jing ; Qing, Tingting ; Sun, Xiaoning ; Zhang, Peng ; Ding, Mingxiao ; Li, Dongsheng ; Deng, Hongkui
刊名细胞研究英文版
2007
关键词human embryonic stem cell direct differentiation insulin-producing cell diabetes RETINOIC ACID DEFINITIVE ENDODERM PANCREATIC-ISLETS DIABETES-MELLITUS HUMAN BLASTOCYSTS MUTANT MICE BETA-CELLS ACTIVIN-A DIFFERENTIATION CULTURE
DOI10.1038/cr.2007.28
英文摘要The capacity for self-renewal and differentiation of human embryonic stem (ES) cells makes them a potential source for generation of pancreatic beta cells for treating type I diabetes mellitus. Here, we report a newly developed and effective method, carried out in a serum-free system, which induced human ES cells to differentiate into insulin-producing cells. Activin A was used in the initial stage to induce definitive endoderm differentiation from human ES cells, as detected by the expression of the definitive endoderm markers Sox17 and Brachyury. Further, all-trans retinoic acid (RA) was used to promote pancreatic differentiation, as indicated by the expression of the early pancreatic transcription factors pdx1 and hlxb9. After maturation in DMEM/F12 serum-free medium with bFGF and nicotinamide, the differentiated cells expressed islet specific markers such as C-peptide, insulin, glucagon and glut2. The percentage of C-peptide-positive cells exceeded 15%. The secretion of insulin and C-peptide by these cells corresponded to the variations in glucose levels. When transplanted into renal capsules of Streptozotocin (STZ)-treated nude mice, these differentiated human ES cells survived and maintained the expression of beta cell marker genes, including C-peptide, pdx1, glucokinase, nkx6.1, IAPP, pax6 and 7cf1. Thirty percent of the transplanted nude mice exhibited apparent restoration of stable euglycemia.; and the corrected phenotype was sustained for more than six weeks. Our new method provides a promising in vitro differentiation model for studying the mechanisms of human pancreas development and illustrates the potential of using human ES cells for the treatment of type I diabetes mellitus.; Cell Biology; SCI(E); PubMed; 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); 166; ARTICLE; 4; 333-344; 17
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/345606]  
专题生命科学学院
推荐引用方式
GB/T 7714
Jiang, Wei,Shi, Yan,Zhao, Dongxin,et al. In vitro derivation of functional insulin-producing cells from human embryonic stem cells[J]. 细胞研究英文版,2007.
APA Jiang, Wei.,Shi, Yan.,Zhao, Dongxin.,Chen, Song.,Yong, Jun.,...&Deng, Hongkui.(2007).In vitro derivation of functional insulin-producing cells from human embryonic stem cells.细胞研究英文版.
MLA Jiang, Wei,et al."In vitro derivation of functional insulin-producing cells from human embryonic stem cells".细胞研究英文版 (2007).
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