Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice.

TLDR

Embryonic stem cells can differentiate into diverse cell types in vitro. Using a cell‑trapping system with insulin‑gene‑driven neomycin and hygromycin selection, the authors derived an insulin‑secreting clone (IB/3x‑99) and implanted 1 × 10⁶ of its clusters into the spleen of diabetic mice. The IB/3x‑99 clone secreted insulin in response to secretagogues, and transplantation of 1 × 10⁶ cells into diabetic mice normalized blood glucose within a week, restored body weight in four weeks, and demonstrated comparable post‑meal glucose control, suggesting a promising alternative to gene therapy for diabetes.

Abstract

Embryonic stem (ES) cells display the ability to differentiate in vitro into a variety of cell lineages. Using a cell-trapping system, we have obtained an insulin-secreting cell clone from undifferentiated ES cells. The construction used allows the expression of a neomycin selection system under the control of the regulatory regions of the human insulin gene. The chimeric gene also contained a hygromycin resistance gene (pGK-hygro) to select transfected cells. A resulting clone (IB/3x-99) containing 16.5 ng/microg protein of total insulin displays regulated hormone secretion in vitro in the presence of various secretagogues. Clusters obtained from this clone were implanted (1 x 10(6) cells) in the spleen of streptozotocin-induced diabetic animals. Transplanted animals correct hyperglycemia within 1 week and restore body weight in 4 weeks. Whereas an intraperitoneal glucose tolerance test showed a slower recovery in transplanted versus control mice, blood glucose normalization after a challenge meal was similar. This approach opens new possibilities for tissue transplantation in the treatment of type 1 and type 2 diabetes and offers an alternative to gene therapy.