Insulin Producing Cells Derived from Human Marrow Stromal Cells

Pluri-potent bone marrow stromal cells (MSCs) are an excellent cell source for unlimited surrogate insulin-producing cells for the treatment of diabetes. We explored this potential of human MSCs (hMSCs) through a non-viral genetic reprogramming approach. Two hMSC lines were transfected with IPF1, NeuroD1 and Ngn3, followed by differentiation induction in vitro and transplantation into diabetic mice. Human MSCs expressed insulin in vitro, but were not glucose responsive. Following transplantation, hMSCs differentiated further and >12% grafted cells expressed insulin and seemed to be glucose responsive. Diabetic mice transplanted with manipulated hMSCs showed reduced blood glucose levels (7.63mM). Most mice became normoglycaemic (6.9+/-0.64mM). Our data confirm that hMSCs can be induced to express insulin sufficient to reverse diabetes in a mouse model. Our triple gene approach has created cells that seem less glucose responsive in vitro but which become more efficient after transplantation.