Hybrid Congregation of Islet Single Cells and Curcumin-Loaded Polymeric Microspheres as an Interventional Strategy to Overcome Apoptosis Associated with Pancreatic Islets Transplantation

Hypoxic or near-anoxic conditions that occur in the core of transplanted islets induce necrosis and apoptosis during the early stages after transplantation, primarily due to loss of vascularization during the isolation process. Moreover, secretion of various cytokines from pancreatic islets is detrimental to the viability of islet cells in vitro. In this study, we aimed to protect pancreatic islet cells against apoptosis by establishing a method for in situ delivery of curcumin to the pancreatic islets. Self-assembled heterospheroids composed of pancreatic islet cells and curcumin-loaded polymeric microspheres were prepared by the three-dimensional cell culture technique. Release of curcumin in the microenvironment of pancreatic islets promoted survival of the islets. In hypoxic culture conditions, which mimic the in vivo conditions after transplantation, viability of the islets was significantly improved, as indicated by a decreased expression of pro-apoptotic protein and an increased expression of anti-apoptotic protein. Additionally, oxidative stress-induced cell death was suppressed. Thus, unlike co-transplantation of pancreatic islets and free microspheres, which provided a wide distribution of microspheres throughout the transplanted area, the heterospheroid transplantation resulted in colocalization of pancreatic islet cells and microspheres, thereby exerting beneficial effects on the cells.