Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells

Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow‐derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin‐producing cells by introduction of the pancreatic duodenal homeobox‐1 (PDX‐1). Recombinant adenoviral vector was used to deliver PDX‐1 gene into hMSCs. After being infected with Ad‐PDX‐1, hMSCs were successfully induced to differentiate into insulin‐secreting cells. The differentiated PDX‐1+ hMSCs expressed multiple islet‐cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C‐peptide in a weak glucose‐regulated manner. After the differentiated PDX‐1+ hMSCs were transplanted into STZ‐induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes. J. Cell. Physiol. 211: 36–44, 2007. © 2007 Wiley‐Liss, Inc.