Regulation of cell proliferation using tissue engineering in MIN6 cells

Pancreatic islet transplantation for patients with diabetes mellitus has be en hindered by the problem of donor shortage, as is the case for transplant ation of other organs. Among several measures to overcome this problem, cel l transplantation using xenogenic cell lines has been considered. For the t reatment of diabetic patients, a murine pancreatic beta -cell line MIN6 is a potential source of cell transplant. In order to restrict otherwise unlim ited proliferation of transplanted MIN6 cells, cells are rendered to form s pheroidal aggregates (SMIN6) on nonadherent culture dishes. SMIN6 stopped i ts growth around day 7 with a diameter of 220 +/- 40 mum and kept its size almost constant at least until day 28. SMIN6 cells, however, had reduced re sponsiveness of insulin secretion to glucose concentration compared with MI N6 cells cultured in a monolayer, On the other hand, spheroid MIN6 cells fo rmed in the presence of extracellular matrix gel (SMIN6E) possessed the cap acity for glucose-dependent insulin secretion comparable with conventional MIN6 cells. SMIN6E encapsulated in agarose beads (SMIN6E-B) was also viable for at least 1 month in vitro with a constant diameter and favorable gluco se responsiveness. The development of spheroid-type MIN6 may contribute to the future clinical application of MIN6 or other beta -cell lines for treat ment of diabetes mellitus.