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In vitro derivation of functional insulin-producing cells from human embryonic stem cells

cell Research 2007年第4期17卷 333-344页

作者： wei jiang~(1,*) yan shi~(1,5,*) dongxin zhao~1 song chen~1 jun yong~1 jing zhang~2 tingting qing~1 xiaoning sun~(1,3) peng zhang~1 mingxiao ding~1 dongsheng li~4 hongkui deng~(1,2,3) ~1department of cell biology and genetics,college of life sciences,peking university,beijing 100871,china ~2beijing Laboratory Animals Research Center,beijing 100012,china ~3Laboratory of Chemical Genomics,Shenzhen Graduate School of peking Universit,the university Town,Shenzhen 518055,china ~4provincial Kev Laboratory of Embryonic Stem cell Research,Tai-He Hospital Yunyang Medical college,32 S.Renmin Rd.,shiyan 442000,china department of cell biology and genetics College of Life Sciences Peking University Beijing China 5Present address: The Scripps Research Institute Chemistry Department SP3130 10550 North Torrey Pines Road La Jolla CA USA. beijing Laboratory Animals Research Center Beijing China Laboratory of Chemical Genomics Shenzhen Graduate School of Peking University the University Town Shenzhen China Provincial Key Laboratory of Embryonic Stem cell Research Tai-He Hospital Yunyang Medical College Shiyan China

The capacity for self-renewal and differentiation of human embryonic stem(ES)cells makes them a potential source forgeneration of pancreatic beta cells for treating type I diabetes ***,we report a newly developed and effectivemethod,carried out in a serum-free system,which induced human ES cells to differentiate into insulin-producing *** A was used in the initial stage to induce definitive endoderm differentiation from human ES cells,as detectedby the expression of the definitive endoderm markers Sox 17 and ***,all-trans retinoic acid(RA)wasused to promote pancreatic differentiation,as indicated by the expression of the early pancreatic transcription factorspdr1 and *** maturation in DMEM/F12 serum-free medium with bFGF and nicotinamide,the differentiatedcells expressed islet specific markers such as C-peptide,insulin,glucagon and *** percentage of C-peptide-posi-tive cells exceeded 15%.The secretion of insulin and C-peptide by these cells corresponded to the variations in *** transplanted into renal capsules of Streptozotocin(STZ)-treated nude mice,these differentiated human EScells survived and maintained the expression of beta cell marker genes,including C-peptide,pdx1,glucokinase,nkx6.1,IAPP,pax6 and *** percent of the transplanted nude mice exhibited apparent restoration of stable euglycemia;and the corrected phenotype was sustained for more than six *** new method provides a promising in vitro dif-ferentiation model for studying the mechanisms of human pancreas development and illustrates the potential of usinghuman ES cells for the treatment of type I diabetes mellitus.

关键词： human embryonic stem cell direct differentiation insulin-producing cell diabetes

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