Co-encapsulation of mesenchymal stromal cells to enhance islet function

Abstract Pericapsular fibrotic overgrowth (PFO) is associated with poor survival of encapsulated islets. A strategy to overcome PFO and improve islet function is co-encapsulation with mesenchymal stromal cells (MSC), which have both immunomodulatory and regenerative properties. MSC co-encapsulation did not alter islet viability and significantly improved islet metabolic function. Preconditioning MSC with a pro-inflammatory cytokine cocktail prior to transplantation enhanced their immunosuppressive potential by inducing nitric oxide and by increasing the secretion of immunomodulatory cytokines. MSC co-encapsulation significantly reduced PFO and improved islet graft survival in syngeneic, allogeneic, and xenogeneic transplantation setting with a better outcome seen with preconditioned MSC. Peritoneal lavage demonstrated higher levels of immunomodulatory cytokines such as IL-4, IL-6, IL-10, and IL-13 in the MSC co-encapsulated groups compared to encapsulated islets alone. In summary, preconditioning MSC enhanced their immunosuppressive potential and MSC co-encapsulation improved islet survival by modulating the immune response and reducing PFO.