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یکشنبه 23 آذر 1404
Cell Journal
، جلد ۱۶، شماره Suppl ۱، صفحات ۸۰-۸۰
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عنوان انگلیسی
Ps-48: Co-Transplantation of Pancreatic Islets and VEGF-Expressing Human Embryonic Stem Cell Derived Mesenchymal Stem Cells through Hydrogel to Ameliorate Alloxan Induced Diabetes in Nude Mice
چکیده انگلیسی مقاله
Objective: Pancreatic islet transplantation has emerged as a promising treatment for type I diabetes, a global health concern with increasing worldwide incidence of 3% per year. However, its efficacy is severely hampered due to poor islet engraftment and revascularization, which have been resulted to partially loss of transplanted islets. It has been shown that local delivery of vascular endothelial growth factor (VEGF) could accelerate transplanted islet revascularization, although permanent high level of VEGF may lead to undesirable side effects. In this study we investigated the effects of conditional cell-based delivery of VEGF through collagen- fibrin hydrogel on transplanted islet function and revascularization. Materials and Methods: RH6 human embryonic stem cell derived mesenchymal stem cells (hESCMSCs) have been transduced by two lentiviruses containing rtTA and VEGF-A. Tet-on expression of VEGF from these cells was shown by tube formation assay and was confirmed through VEGF ELISA. After cotransplantation of these cells and mouse isolated islets through collagen-fibrin hydrogel in the omental pouch of diabetic nude mice, the blood glucose, body weight, glucose tolerance and serum C-peptide was measured after 28 days. As control groups, islets were transplanted alone and with non-transgenic hESC-MSCs. Results: Function of islets transplanted with hESCMSC: VEGF in presence of Dox induction was significantly improved, accompanied with superior islet revascularization demonstrated by enhancement in micro- vessel density and area per vessel, compared with control groups. Conclusion: We conclude that conditional expression of VEGF from hESC-MSCs during islet transplantation could enhance islet functionality and revascularization. This result can be used to improve the outcome of clinical islet transplantation.
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http://celljournal.org/journal/article/abstract/374
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