Development of polyvinyl alcohol bioartificial pancreas with rat islets and mesenchymal stem cells

Abstract

To improve the function of the polyvinyl alcohol (PVA) bioartificial pancreas, we focused on bone marrow-derived mesenchymal stem cells (MSCs). We examined whether the function of PVA-encapsulated rat islets could be improved by coencapsulation with syngeneic MSCs. We macroencapsulated 1,500 rat islet equivalents (IEQ) with or without 1 × 10(6) MSCs with the use of 3% PVA solution before implantation intraperitoneally into diabetic BALB/c mice. We evaluated the function of the device in vitro (the residual rate, viability, and insulin-releasing function of the islets) and in vivo assessments (blood glucose and serum C-peptide changes after transplantation and glucose tolerance test). Although cultured islets also were destroyed, the shapes of the islets cocultured with MSCs were preserved but not different from encapsulated islets without MSCs. At 96 hours after culture the residual rates of islet recovery among those cocultured with versus without MSCs were 66% versus 39.5%, respectively, (P = .03). On the other hand, there was no significant difference between encapsulated islets with versus without MSCs. Furthermore, the stimulation index of the islets was improved by coculture with MSCs (2.6 ± 0.6 vs 1.4 ± 0.1; P = .03), but no beneficial effects were observed between islets encapsulated with versus without MSCs. The viability of islets cocultured with MSCs was significantly better than that without MSCs (84.2 ± 2.5 vs 73.3 ± 0.9; P = .037), but MSCs did not improve the viability of encapsulated islets. There were no significant differences in blood glucose or serum C-peptide between islets encapsulated with versus without MSCs. The histologic findings showed many degenerative islets and MSCs soon after transplantation. In conclusion, further studies are necessary to develop a novel PVA bioartificial pancreas that can be used with MSCs.