Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space

Beta cell replacement therapy (BCRT) for patients with type 1 diabetes (T1D) improves blood glucose regulation by replenishing the endogenous beta cells destroyed autoimmune attack. Several limitations, including immune isolation, prevent this from reaching its full potential. Cell encapsulation devices used BCRT provide a protective physical barrier insulin-producing cells, thereby protecting transplanted However, poor device engraftment posttransplantation leads to nutrient deprivation and hypoxia, causing metabolic strain on cells. Prevascularization of at transplantation site can help establish host vascular network around implant, increasing solute transport encapsulated Here, we present replenishable prevascularized implantation methodology (RPVIM) that allows integration in subcutaneous space. Empty were vascularized 14 days, after which inserted without disrupting surrounding vasculature. The RPVIM compared nonprevascularized (Standard Implantation Methodology [SIM]) previously established [SPVIM]). Results show over 75% containing stem cell-derived clusters showed signal 28 days Notably, not only was percent showing significantly greater than SIM SPVIM devices, but intraperitoneal tolerance tests histological analyses stem-cell derived retained their function is crucial successful management T1D.