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• W2094161245 abstract "Type 1 diabetes is an autoimmune disease caused by permanent destruction of insulin-producing pancreatic β cells and requires lifelong exogenous insulin therapy. Recently, islet transplantation has been developed, and although there have been significant advances, this approach is not widely used clinically due to the poor survival rate of the engrafted islets. We hypothesized that improving survival of engrafted islets through ex vivo genetic engineering could be a novel strategy for successful islet transplantation. We transduced islets with adenoviruses expressing betacellulin, an epidermal growth factor receptor ligand, which promotes β-cell growth and differentiation, and transplanted these islets under the renal capsule of streptozotocin-induced diabetic mice. Transplantation with betacellulin-transduced islets resulted in prolonged normoglycemia and improved glucose tolerance compared with those of control virus-transduced islets. In addition, increased microvascular density was evident in the implanted islets, concomitant with increased endothelial von Willebrand factor immunoreactivity. Finally, cultured islets transduced with betacellulin displayed increased proliferation, reduced apoptosis and enhanced glucose-stimulated insulin secretion in the presence of cytokines. These experiments suggest that transplantation with betacellulin-transduced islets extends islet survival and preserves functional islet mass, leading to a therapeutic benefit in type 1 diabetes. Islets transplanted into diabetic mice as a therapeutic measure survive longer if they have been modified to express the growth-promoting protein betacellulin. Byung-Hyun Park and colleagues at the Chonbuk National University Medical School in Jeonju, South Korea, modified rat pancreatic islets to express betacellulin, which promotes regeneration of the insulin-producing β-cells found in islets. The researchers transplanted both engineered and non-engineered islets into mice with chemically induced diabetes. The mice with the betacellulin-expressing islets had higher rates of islet survival, better control of blood sugar levels and elevated blood insulin levels. In cell culture, the manipulated islets also displayed increased growth and enhanced secretion of insulin in the presence of potentially damaging immune molecules known as cytokines. These modified islets could form the basis of a cell therapy for type 1 diabetes." @default.
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• W2094161245 date "2014-05-30" @default.
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• W2094161245 title "Transplantation of betacellulin-transduced islets improves glucose intolerance in diabetic mice" @default.
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• W2094161245 doi "https://doi.org/10.1038/emm.2014.24" @default.
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