Correction of diabetes mellitus by transplanting minimal mass of syngeneic islets into vascularized small intestinal segment.
2013
Center of Tissue Engineering, Ilia State University,Tbilisi, Georgia*Corresponding author: Ekaterine Berishvili,eberishvili@gmail.comTransplantation of mature islets into portal vein hasbeen most effective thus far, although attrition oftransplanted islets constitutes a major limitation, andalternative approaches are required. We analyzed themechanisms by which islets engrafted, vascularizedand functioned over the long term in the smallintestinal submucosa. To determine engraftment,survival and function, 350 syngenic islets were trans-plantedintoeitherintestinalsegmentsorportalveinofdiabetic rats. Islet reorganization, vascularization andfunction were analyzed by histological analysis, RT-PCR analysis as well as glycemic control over up to1 year. Transplantation of syngeneic islets in marginalnumbers successfully restored normoglycemia indiabetic rats. Transplantation of semi-pure islet prepa-rationdidnotimpairtheirengraftment,vascularizationand function. Islets were morphologically intact andexpressed insulin as well as glucagon over the year.Expression of angiogenic genes permitted revasculari-zation of transplanted islets. We identified the expres-sion of transcription factors required for maintenanceofbetacells.Thesestudiesdemonstratedthatmarginalmass of transplanted islets was sufficient to restoreeuglycemia in streptozotocin-treated rats. These supe-rior results were obtained despite use of an impurepreparation of islets in animals with small intestinalsegment. Our findings will help advance new horizonsfor cell therapy in patients with diabetes.Keywords: Islets, pancreas, portal vein, small intes-tine, transplantationAbbreviations: bFGF, basic fibroblast growth factor;DAB, 3,3
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