Transplantation of Insulin-Producing Clusters Derived From Adult Bone Marrow Stem Cells to Treat Diabetes in Rats

Abstract

Objectives: Recent findings suggest that bone marrow stem cells can differentiate into numerous cell types. This would provide a potentially unlimited source of isletlike cells for transplantation and a promising therapy for diabetes mellitus. Here, we studied the differentiation ability of adult bone marrow hematopoietic-rich stem cells to form glucose-regulating insulin-producing cells. Their ability to treat chemically induced diabetes in rats was then tested.

Materials and Methods: Hematopoietic-rich stem cells were obtained from the long bones of rats and cultured in a serum-free medium containing 1% dimethyl sulfoxide for 3 days. The cells were cultured for 7 days in a glucose-rich medium supplemented with pancreatic extract. Thereafter, cultures were done in a medium (low concentration of glucose and 5% fetal bovine serum) supplemented with nicotinamide and exendin-4 for 7 more days.

Results: At day 17 of culture, the cells formed isletlike clusters. These were distinctly stained crimson red by diphenylthiocarbazone and expressed insulin and endocrine-specific trans­cription genes. Insulin was secreted in a dose-response manner as a function of increasing glucose concentrations. When transplanted in the testes of diabetic rats, the differentiated cells could normalize blood glucose levels for 3 months in 80% of the treated rats. The therapeutic benefits were reversed after orchidectomy.

Conclusions: Hematopoietic-rich stem cells may include pancreatic progenitor cells capable of differentiating into functioning endocrine hormone-producing cells. This finding suggests a possible means of treating diabetes mellitus.