Abstract
BACKGROUND: Embryonic stem cell (ESC)-derived β cells hold the promise of providing a renewable source of tissue for the treatment of insulin-dependent diabetes. Encapsulation may allow ESC-derived β cells to be transplanted without immunosuppression, thus enabling wider application of this therapy. METHODS: In this study, we investigated the immunogenicity of mouse pancreatic progenitor cells and efficacy of a new macroencapsulation device in protecting these cells against alloimmune and autoimmune responses in mouse models. RESULTS: Mouse pancreatic progenitor cells activated the indirect but not the direct pathway of alloimmune response and were promptly rejected in immune competent hosts. The new macroencapsulation device abolished T cell activation induced by allogeneic splenocytes and protected allogeneic MIN6 β cells and pancreatic progenitors from rejection even in presensitized recipients. In addition, the device was effective in protecting MIN6 cells in spontaneously diabetic nonobese diabetic recipients against both alloimmune and recurring autoimmune responses. CONCLUSIONS: Our results demonstrate that macroencapsulation can effectively prevent immune sensing and rejection of allogeneic pancreatic progenitor cells in fully sensitized and autoimmune hosts.