| Induction of insulin-producing cells derived from endometrial mesenchymal stem-like cells. | |
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MedLine Citation:
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PMID: 20855446 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Studies have demonstrated that mesenchymal stem-like cells can be isolated from endometrium. However, the potential of endometrial-derived stem cells to differentiate into insulin-positive cells and functionally secrete insulin remains undetermined. We isolated endometrial mesenchymal stem-like cells (EMSCs) from human endometrial tissue from six donors. The insulin-secreting function of EMSCs was further analyzed in vitro and in transplanted grafts in vivo. We successfully isolated EMSCs from human endometrium, and our results showed that EMSCs expressed high levels of stemness genes (Nanog, Oct-4, Nestin). Under specific induction conditions for 2 weeks, EMSCs formed three-dimensional spheroid bodies (SBs) and secreted C-peptide. The high insulin content of SB-EMSCs was confirmed by enzyme-linked immunosorbent assay, and glucose responsiveness was demonstrated by measuring glucose-dependent insulin secretion. Using cDNA microarrays, we found that the expression profiles of SB-EMSCs are related to those of islet tissues. Insulin and C-peptide production in response to glucose was significantly higher in SB-EMSCs than in undifferentiated EMSC controls. Furthermore, upon differentiation, SB-EMSCs displayed increased mRNA expression levels of NKx2.2, Glut2, insulin, glucagon, and somatostatin. Our results also showed that SB-EMSCs were more resistant to oxidative damage and oxidative damage-induced apoptosis than fibroblasts from the same patient. It is noteworthy that SB-EMSCs xenotransplanted into immunocompromised mice with streptozotocin-induced diabetes restored blood insulin levels to control values and greatly prolonged the survival of graft cells. These data suggest that EMSCs not only play a novel role in the differentiation of pancreatic progenitors, but also can functionally enhance insulin production to restore the regulation of blood glucose levels in an in vivo transplantation model. |
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Authors:
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Hsin-Yang Li; Yi-Jen Chen; Shih-Jen Chen; Chung-Lan Kao; Ling-Ming Tseng; Wen-Liang Lo; Chia-Ming Chang; Der-Ming Yang; Hung-Hai Ku; Nae-Fang Twu; Chen-Yi Liao; Shih-Hwa Chiou; Yuh-Lih Chang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-20 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 335 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 817-29 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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