Construction of PLGA Porous Microsphere-Based Artificial Pancreatic Islets Assisted by the Cell Centrifugation Perfusion Technique

Abstract

Pancreatic islet transplantation is a promising treatment that could potentially reverse diabetes, but its clinical applicability is severely limited by a shortage of organ donors. Various cell loading approaches using polymeric porous microspheres (PMs) have been developed for tissue regeneration; however, PM-based multicellular artificial pancreatic islets’ construction has been scarcely reported. In this study, MIN6 (a mouse insulinoma cell line) and MS1 (a mouse pancreatic islet endothelial cell line) cells were seeded into poly(lactic-co-glycolic acid) (PLGA) PMs via an upgraded centrifugation-based cell perfusion seeding technique invented and patented by our group. Cell morphology, distribution, viability, migration, and proliferation were all evaluated. Results from glucose-stimulated insulin secretion (GSIS) assay and RNA-seq analysis suggested that MIN6 and MS1-loaded PLGA PMs exhibited better glucose responsiveness, which is partly attributable to vascular formation during PM-dependent islet construction. The present study suggests that the PLGA PM-based artificial pancreatic islets may provide an alternative strategy for the potential treatment of diabetes in the future.