Co-transplantation with mesenchymal stem cells and endothelial cells improvise islet engraftment and survival in STZ treated hyperglycemic mice

Abstract

AbstractThough intra-portal islet transplantation demonstrated as best suited strategy for the reversal of hyperglycemia without the threat of iatrogenic hyperglycemia in type 1 diabetes (T1D) in patients, the inferior quality of post-transplantation (tx) vascularization needs to be addressed for the maximization of post-tx islet survival. Therefore, in this study, we have first generated MSCs and endothelial progenitor cells (EPC) from mice bone marrow by in house optimized protocol and then 3-D co-cultured them with mice islets. Secretion of in the culture supernatant suggested the pro-angiogenic nature of 3D cultured mice islets. After 5 days post-tx of these pro-angiogenic islets in the omental pouch of syngeneic mice led to: 1) restoration of normoglycemia, 2) secretion of mouse C-peptide and 3) induction of angiogenic factors after 3 days of post-tx. The induction of angiogenic factors was done by RT-qPCR of omental biopsies. Importantly, pro-angiogenic islet recipient mice also demonstrated the clearance of glucose within 75 min, reflecting their efficient function and engraftment. Our results highlights needs of 3-D co-culture islets for superior quality post-tx islet vasculature and better engraftment – crux to improvise the challenges associated with post-tx islet vascularization and functions.