Molecular engineering human hepatocytes into pancreatic beta cells for diabetes therapy

Type 1 (formerly “juvenile”) diabetes is believed to be an autoimmune disease in which host immune cells fail to recognize the insulin-producing beta cells contained within pancreatic islets of Langerhans as being “self” and inappropriately elect to destroy these critical insulin-producing cells. The traditional methods of treating type 1 diabetes are good, but not perfect. The studies reported by Sapir et al. (1) in this issue of PNAS suggest that new, more acceptable approaches to beta cell replacement may be feasible. In the current treatment of type 1 diabetes, insulin is given by injection or insulin pump. Patients must frequently check their blood glucose by finger stick to calculate and adjust their insulin doses. Undertreatment (hyperglycemia) and overtreatment (hypoglycemia) are common. The ideal therapy for diabetes would mimic the two essential features of normal beta cells: the ability to sense glucose continually coupled with intelligent and appropriate release of insulin in response to changes in blood glucose. One solution could be an implantable, glucose-sensing insulin delivery system. Attempts to develop such a computer-driven, “closed-loop” insulin delivery system have been aided substantially by the miniaturization of computer chips and insulin pumps. Important hurdles relate to development of reliable, long-term glucose sensors, miniaturization, replacement of batteries, and refillable reservoirs for the necessary insulin pumps. Whole pancreas transplant is another option. Long-term graft function is excellent, but the procedure requires major surgery, is limited by the small numbers of pancreata available for transplant, and is accompanied by morbidity from immunosuppressive drugs used to prevent organ rejection (2). In 2000, a group in Edmonton, Canada, demonstrated the feasibility of pancreatic islet transplantation (3), which requires only trivial outpatient surgery. The Edmonton demonstration that long-term islet graft survival and function are possible has reinvigorated attempts at beta cell replacement therapy. In broad terms, there are …