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• W2427433249 endingPage "2082" @default.
• W2427433249 startingPage "2077" @default.
• W2427433249 abstract "In Brief Background Muscle is a promising alternative site for islet transplantation that facilitates rapid restoration of islet vascularization. However, the development of fibrosis suggests massive cellular death after transplantation. This study tested the hypothesis that islet graft function is limited by hypoxia-related death early after intramuscular transplantation, but that this can be overcome by cotransplantation of an oxygen carrier, that is, polymerized bovine hemoglobin (PolyHb). Methods Two hundred islets were transplanted with or without different doses of PolyHb intramuscularly to nondiabetic C57BL/6 and diabetic C57BL/6 nu/nu mice. β-cell hypoxia and apoptosis were evaluated by immunohistochemistry after injection of the biochemical marker pimonidazole or by staining for caspase-3, respectively. Blood glucose concentrations were monitored for 30 days after islet transplantation and animals were then subjected to an intravenous glucose tolerance test. Results Substantial hypoxia was observed in control islet grafts during the first 4 days after transplantation. Cotransplantation of PolyHb resulted in a dose-dependent reduction of β-cell hypoxia, but β-cell apoptosis was only reduced by cotransplantation of low-dose PolyHb (0.03 mg/g body weight) due to the inflammatory effects of higher PolyHb concentrations. Cotransplantation of low-dose PolyHb resulted in improved islet graft function 30 days after transplantation in diabetic mice, with a glucose tolerance comparable to transplantation of 50% more islets. Conclusion We conclude that cotransplantation of islets with PolyHb can be used to effectively bridge the critical hypoxic phase immediately after transplantation, improve islet graft function, and reduce the number of islets needed for successful intramuscular transplantation. In islet transplantation, muscle is tested as an alternative site for transplantation. In this article, the authors report that co-transplantation of islets with the oxygen carrier PolyHb, effectively counteracts the deficits of islet oxygen deprivation and improves their graft function." @default.
• W2427433249 created "2016-06-24" @default.
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• W2427433249 date "2015-10-01" @default.
• W2427433249 modified "2023-09-27" @default.
• W2427433249 title "Cotransplantation of Polymerized Hemoglobin Reduces β-Cell Hypoxia and Improves β-Cell Function in Intramuscular Islet Grafts" @default.
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• W2427433249 doi "https://doi.org/10.1097/tp.0000000000000815" @default.
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• W2427433249 hasPublicationYear "2015" @default.
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