Intrasplenic Transplantation of Encapsulated Genetically Engineered Mouse Insulinoma Cells Reverses Streptozotocin-Induced Diabetes in Rats (original) (raw)

2005, Cell Transplantation

Pancreatic islet transplantation is limited by shortage of donor organs. Although β-cell lines could be used, their secretion of insulin is characteristically glucose independent and immunoisolation is required. Here we show that intrasplenic transplantation of encapsulated glucose-responsive mouse insulinoma cells reversed streptozotocin (STZ)-induced diabetes in rats. MIN-6 cells derived from a transgenic mouse expressing SV 40 large T antigen in pancreatic β-cells were transfected with minigene encoding for human glucagon-like-peptide-1 under the control of rat insulin promoter. The cells were encapsulated in alginate/poly-L-lysine and used for cell transplantation in STZ-diabetic rats. Rats with nonfasting blood glucose (n-FBG) greater than 350 mg/dl were used. In group I rats (n = 6) 20 million encapsulated cells were injected into the spleen. Group II rats (n = 6) received empty capsules. n-FBG was measured biweekly. After 4 and 8 weeks, an intraperitoneal glucose tolerance te...