RGD-Containing Elastin Like Polypeptide Improves Islet Transplantation Outcomes in Diabetic Mice Via Upregulation of Islet Survival and Vessel Formation

Abstract

Successful islet transplantation critically depends on the isolation of healthy islets. Paradoxically, the islet isolation procedure contributes to islet death due to the destruction of intra- and peri-islet extracellular matrices (ECMs) during digestion. We investigated whether an RGD-containing elastin-like polypeptide named REP as a self-assembling matrix replenish damaged or missing ECMs and protects islet against cell death. Immediately following isolation, islets were coated with REP coacervate particles via isothermal adsorption of REP solution followed by thermal gelation. Both the viability and insulin secretory capacity of REP-coated islets were markedly increased during the pre-transplant culture, whereas control islets progressively lost viability and function. Co-transplantation of REP-treated islets and REP beneath the renal sub-capsule restored normoglycemia and serum insulin levels in streptozotocin-induced diabetic mice. Compared to islet-only transplants, mice that received co-transplants had a longer euglycemia maintenance time, sustained xenogeneic- and syngeneic- graft survival. Moreover, concomitant β-cell proliferation and generation of a rich vasculature were observed at the co-transplantation sites. In conclusion, the REP-based coacervation strategy provides great therapeutic potential for improving the ECMs for graft survival and functions, and most importantly to increase the outcomes of islet transplantation.

Keywords: RGD-containing elastin-like polypeptide, Protein coacervate, Islet transplantation, Islet survival, Insulin secretion