A composite capsule strategy to support longevity of microencapsulated pancreatic β cells

Pancreatic islet microencapsulation allows transplantation of insulin producing cells in absence of systemic immunosuppression, but graft survival is still limited. In vivo studies have demonstrated that many islet-cells die in the immediate period after transplantation. Here we test whether intracapsular inclusion of ECM components (collagen IV and RGD) with necrostatin-1 (Nec-1), as well as amino acids (AA) have protective effects on islet survival. Also, the inclusion of pectin was tested as it enhances the mitochondrial health of beta-cells. To enhance the longevity of encapsulated islets, we studied the impact of the incorporation of the mentioned components into the alginate-based microcapsules in vitro. The efficacy of the different composite microcapsules on MIN6 beta-cell or human islet-cell survival and function, as well as suppression of DAMP-induced immune activation, were determined. Finally, we examined the mitochondrial dynamic genes. This was done in the absence and presence of a cytokine cocktail. Here, we found that composite microcapsules of APENAA improved insulin secretion and enhanced the mitochondrial activity of beta-cells. Under cytokine exposure, they prevented the cytokine-induced decrease of mitochondrial activity as well as viability till day 5. The rescuing effects of the composite capsules were accompanied by alleviated mitochondrial dynamic gene expression. The composite capsule strategy of APENAA might support the longevity of microencapsulated beta-cells by lowering susceptibility to inflammatory stress. Our data demonstrate that combining strategies to support beta-cells by changing the intracapsular micro-environment might be an effective way to preserve islet graft longevity in the immediate period after transplantation.