|Budget Amount *help
¥46,670,000 (Direct Cost: ¥35,900,000、Indirect Cost: ¥10,770,000)
Fiscal Year 2012: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2011: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2010: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2009: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Islet transplantation can induce a substantial improvement in the treatment of type 1 diabetes mellitus (DM). However, the clinical application of islet transplantation is severely limited by the shortage of donor organs. We describe the generation of beta-cell spheroids using mouse insulinoma cells (MIN6) as a model of beta-cells. We established a 3D culture system that simulates microgravity using a 3D clinostat. Using this method, we were able to produce 100 spheroids per mL of culture media. The spheroids produced in the clinostat expressed several beta-cell signature genes at higher levels than the levels that were found in MIN6 cultured in a standard 2D culture dish (MIN6-2D). The transplantation of the spheroids into the DM mice ameliorates hyperglycemia, whereas the transplantation of the equivalent number of 2D-cultured cells failed to cure DM. These results indicate that the clinostat culture provides a new method for the reconstitution of a large number of functional beta-cell spheroids for DM treatment.