Vascularization of PLGA-based bio-artificial beds by hypoxia-preconditioned mesenchymal stem cells for subcutaneous xenogeneic islet transplantation

Abstract

Background Subcutaneous tissue is an attractive extra-hepatic heterotopic site for islet transplantation; however, poor oxygen tension and blood supply during early engraftment of implanted islets have limited the use of this site in clinical applications. Methods This study investigated the vascularization potential of hypoxia-preconditioned mesenchymal stem cells (3% O-2; hypo-MSCs) in PLGA-based bio-artificial beds for subsequent subcutaneous islet transplantation. Sheet-typed polymeric PLGA scaffolds coated with hypo-MSCs or normo-MSCs (MSCs cultured under normoxia conditions, 21% O-2) were implanted subcutaneously in mice. Results Compared to normo-MSCs, hypo-MSCs significantly enhanced vasculogenesis, both on the interior and exterior surfaces of the implanted PLGA devices, which peaked 4 weeks after implantation. Further, infusion of porcine islets inside the prevascularized PLGA bed restored normal glycemic control in 6 of 6 STZ-induced diabetic mice. The mass of the marginal islet was approximately 2000 IEQs, which is comparable to that required for the renal subcapsular space, a highly vascularized site. Conclusions Therefore, PLGA-based bio-artificial devices prevascularized with hypo-MSCs could be a useful modality for successful subcutaneous islet transplantation, which is of high clinical relevance.