The beneficial Effects of Neural Crest Stem Cells on Pancreatic      ?–cells

Abstract: Patients with type-1 diabetes lose their ?-cells after autoimmune attack. Islet transplantation is a co-option for curing this disease, but survival of transplanted islets is poor. Thus, methods to enhance ?-cell viability and function as well as methods to expand ?-cell mass are required. The work presented in this thesis aimed to study the roles of neural crest stem cells or their derivatives in supporting ?-cell proliferation, function, and survival.In co-culture when mouse boundary cap neural crest stem cells (bNCSCs) and pancreatic islets were in direct contact, differentiating bNCSCs strongly induced ?-cell proliferation, and these proliferating ?-cells were glucose responsive in terms of insulin secretion. Moreover, co-culture of murine bNCSCs with ?-cell lines RIN5AH and ?-TC6 showed partial protection of ?-cells against cytokine-induced ?-cell death. Direct contacts between bNCSCs and ?-cells increased ?-cell viability, and led to cadherin and ?-catenin accumulations at the bNCSC/?-cell junctions. We proposed that cadherin junctions supported signals which promoted ?-cell survival. We further revealed that murine neural crest stem cells harvested from hair follicles were unable to induce ?-cell proliferation, and did not form cadherin junctions when cultured with pancreatic islets. Finally, we discovered that the presence of bNCSCs in co-culture counteracted cytokine-mediated insulin-producing human EndoC-?H1 cell death. Furthermore, these two cell types formed N-cadherin, but not E-cadherin, junctions when they were in direct contact. In conclusion, the results of these studies illustrate how neural crest stem cells influence ?-cell proliferation, function, and survival which may improve islet transplantation outcome.