Human iPS Cell-Derived Insulin Producing Cells Form Vascularized Organoids under the Kidney Capsules of Diabetic Mice
Figure 4
IPCs correct hyperglycemia in diabetic mice.
A) Eight weeks old Rag2−/−γc−/− mice were made diabetic following streptozotocin treatment. The pre-transplant blood levels were >400 mg/dl. Approximately 5×106 human iPS cell-derived IPCs were transplanted under the kidney capsule of each mouse. The blood glucose levels were monitored for >100 days. Blood glucose levels with peak and trough kinetics were observed throughout the duration of the study. The normalization of blood glucose levels was observed in 3 out of 5 mice. The remaining 2 were borderline diabetic. B) To study whether the transplanted mice could control high sugar levels, we performed the glucose tolerance test. Mice that had become normoglycemic were subjected to intra-peritoneal glucose tolerance test. The normal healthy control mice displayed a faster blood glucose clearance while the mice transplanted with human iPS cell-derived IPCs had a slightly impaired glucose tolerance. C) To rule out that the pancreata of streptozotocin-treated mice did not regenerate, we sacrificed the transplanted mice and histologically examined the pancreas. Streptozotocin-treated mice that had received HPCs did not have any pancreatic islets left.