Improving the function of islet and beta-cell grafts

• Main Author: Paget, Michelle B.
• Published: Aston University 2008
• Subjects: 617.557; Biological Sciences
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497373

Human islet transplantation would offer a less invasive and more physiological alternative than whole pancreas transplantation and insulin injections respectively for the treatment of diabetes mellitus if islet graft survival can be improved, initial recipient post-transplant insulin independence declines to <10% after 5 years. Factors contributing to graft failure include enzymatic disruption of the islet microenvironment during isolation, diabetogenic effects of immunosuppressants and metabolic stress resulting from slow revascularisation. Aims: To investigate the effect of co-culture in both static (SC) and rotational culture (RC) of BRINBDU beta-cells (Dl 1) and human umbilical vein endothelial cells (HUVEC) on D11 insulin secretion; and the effect of a thiazolidmedione (TZD) on Dl 1 function and HUVEC proliferation. To assess the effect of culture media, SC, RC and a TZD on human islet morphology, insulin secretion and VEGF production. To initiate in vivo protocol development for assessment of revascularisation of human islet grafts.