Generation of Insulin‐Producing Cells from Human Bone Marrow Mesenchymal Stem Cells by Genetic Manipulation

β Cell replacement is a promising approach for treatment of type 1 diabetes; however, it is limited by a shortage of pancreas donors. The pluripotent MSC in adult bone marrow (BM) offer an attractive source of stem cells for generation of surrogate β cells. BM‐MSC can be obtained with relative ease from each patient, allowing potential circumvention of allograft rejection. Here, we report a procedure for expansion of BM‐MSC in vitro and their differentiation into insulin‐producing cells. The pancreatic duodenal homeobox 1 (Pdx1) gene was expressed in BM‐MSC from 14 human donors, and the extent of differentiation of these cells toward the β‐cell phenotype was evaluated. RNA and protein analyses documented the activation of expression of all four islet hormones. However, the cells lacked expression of NEUROD1, a key transcription factor in differentiated β cells. A significant insulin content, as well as glucose‐stimulated insulin release, were demonstrated in vitro. Cell transplantation into streptozotocin‐diabetic immunodeficient mice resulted in further differentiation, including induction of NEUROD1, and reduction of hyperglycemia. These findings were reproducible in BM‐MSC from 9 of 14 donors of both sexes, ages 19–62. These results suggest a therapeutic potential for PDX1‐expressing BM‐MSC in β‐cell replacement in patients with type 1 diabetes. Disclosure of potential conflicts of interest is found at the end of this article.