Feasibility Study On Allogeneic And Xenogeneic Islet Transplantation Based On Tissue Engineering Prevascularization

Type 1 diabetes is an autoimmune disease and mainly depend on insulin injection to control by hyperglycosemia.However,injection of insulin alone could not prevent the occurrence of diabetic complications and may take the risk of hypoglycemia.Although islet transplantation provides an attractive approach for treatment diabetes,the survival and function of pancreatic islet in homing locations still remain unsatisfied.One of possible reasons that accounts for this is local hypoxiamas a result of shortage of blood supply.The development of biomaterials provides a new approach for islet transplantation.Here we described a pre-vascularized tissue engineering chambers(TECs)which filled Matrigel~TMM and bFGF-2 in the groin of diabetic mice.The study aims to explore the feasibility of syngeneic,allogeneic and xenogeneic transplantation in TECs for treatment of type 1 dibetes.The study would provide a theoretical method for the application of pre-vascularization chamber as a new islet transplantation site.A highly developed micro-vascularized network was established in the TECs on day 28 post-implantation.The duration that normalization of blood glucose levels of diabetic mice was closely correlated with the days of pre-vascularization.In allogeneic islet transplant setting,all grafts were induced to long-term survival(LTS)by the combination of anti-CD45RB and anti-CD40L,compared to 16 of 20(80%)xenografts with long-term survival in xenogeneic islet transplant setting.For those four of 20(20%)rejected xenografts in xenogeneic model,re-transplantation of xenogeneic islets into the TECs allowed 3 of 4(75%)grafts to survive for long term.Positive insulin was stain by anti-insulin and demonstrated the intact secretive function of islet.The immunohistochemistry showed that islets were not infiltrated by effective T cells which were stained by CD4 and CD8 upon the dual antibodies treatment for 2 weeks.Taken together,these findings highlight that TECs,a novel pre-vascularized construct,could serve as an alternative site for pancreatic islet transplantation,implicating the potential of artificial pancreas application in the future.