| In vitro derivation of functional insulin-producing cells from human embryonic stem cells. | |
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MedLine Citation:
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PMID: 17426693 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 Tcf1. 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. |
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Authors:
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Wei Jiang; Yan Shi; Dongxin Zhao; Song Chen; Jun Yong; Jing Zhang; Tingting Qing; Xiaoning Sun; Peng Zhang; Mingxiao Ding; Dongsheng Li; Hongkui Deng |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell research Volume: 17 ISSN: 1748-7838 ISO Abbreviation: Cell Res. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-04-16 Completed Date: 2007-10-03 Revised Date: 2011-06-01 |
Medline Journal Info:
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Nlm Unique ID: 9425763 Medline TA: Cell Res Country: China |
Other Details:
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Languages: eng Pagination: 333-44 Citation Subset: IM |
Affiliation:
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Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Activins
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pharmacology Animals Biological Markers / metabolism Cell Differentiation / physiology* Culture Media, Serum-Free DNA-Binding Proteins / metabolism Diabetes Mellitus, Experimental / metabolism, therapy Embryonic Stem Cells / cytology*, metabolism, transplantation Endoderm / cytology, metabolism Fetal Proteins / metabolism High Mobility Group Proteins / metabolism Homeodomain Proteins / metabolism Humans Insulin / biosynthesis* Mice Mice, Nude SOXF Transcription Factors T-Box Domain Proteins / metabolism Trans-Activators / metabolism Transcription Factors / metabolism Tretinoin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Brachyury protein; 0/Culture Media, Serum-Free; 0/DNA-Binding Proteins; 0/Fetal Proteins; 0/High Mobility Group Proteins; 0/Homeodomain Proteins; 0/MNX1 protein, human; 0/SOX17 protein, human; 0/SOXF Transcription Factors; 0/T-Box Domain Proteins; 0/Trans-Activators; 0/Transcription Factors; 0/activin A; 0/pancreatic and duodenal homeobox 1 protein; 104625-48-1/Activins; 11061-68-0/Insulin; 302-79-4/Tretinoin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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