| MafA promotes the reprogramming of placenta-derived multipotent stem cells into pancreatic islets-like and insulin+ cells. | |
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MedLine Citation:
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PMID: 20158571 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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MafA is a pancreatic transcriptional factor that controls β-cell-specific transcription of the insulin gene. However, the role of MafA in the regulation of pancreatic transdifferentiation and reprogramming in human stem cells is still unclear. In this study, we investigate the role of MafA in placenta-derived multipotent stem cells (PDMSCs) that constitutively expressed Oct-4 and Nanog. PDMSCs were isolated and transfected with MafA using a lentivector. Our results showed that overexpression of MafA in PDMSCs significantly up-regulated the expression of pancreatic development-related genes (Sox17, Foxa2, Pdx1 and Ngn3). Microarray analysis suggested that the gene expression profile of MafA-overexpressing PDMSCs was similar to that of pancreas and islet tissues. MafA increased the expression levels of the mRNAs of NKx2.2, Glut2, insulin, glucagons and somatostatin, and further facilitated the differentiation of PDMSCs into insulin(+) cells. The glucose-stimulated responses to insulin and c-peptide production in MafA-overexpressing PDMSCs were significantly higher than in PDMSCs with vector control. Our results indicated that MafA-overexpressing PDMSCs were more resistant to oxidative damage and oxidative damage-induced apoptosis than PDMSCs carrying the vector control were. Importantly, the expression of MafA in PDMSCs xenotransplanted into immunocompromised mice improved the restoration of blood insulin levels to control values and greatly prolonged the survival of graft cells in immunocompromised mice with STZ-induced diabetes. In summary, these data suggest that MafA plays a novel role in the reprogramming of stem cells into pancreatic β-progenitors, promotes the islet-like characteristics of PDMSCs, as well as functionally enhances insulin production to restore the regulation of blood glucose levels in transplanted grafts. |
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Authors:
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Shih-Hwa Chiou; Shih-Jen Chen; Yuh-Lih Chang; Yu-Chih Chen; Hsin-Yang Li; Dow-Tien Chen; Hsin-Hui Wang; Chia-Ming Chang; Yi-Jen Chen; Hung-Hai Ku |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular and molecular medicine Volume: 15 ISSN: 1582-4934 ISO Abbreviation: J. Cell. Mol. Med. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101083777 Medline TA: J Cell Mol Med Country: England |
Other Details:
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Languages: eng Pagination: 612-24 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
Affiliation:
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Department & Institute of Pharmacology, Taipei Veterans General Hospital, Taipei, Taiwan. shchiou@vghtpe.gov.tw |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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