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- Title
Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells.
- Authors
Yanhua Li; Haifa Qiao; Rui Zhang; Heping Zhang; Yunfang Wang; Hongfeng Yuan; Qinbin Liu; Daqing Liu; Lin Chen; Xuetao Pei
- Abstract
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.
- Subjects
ISLANDS of Langerhans; TREATMENT of diabetes; ISLANDS of Langerhans transplantation; PANCREATIC beta cells; GLUCAGON
- Publication
Journal of Cellular Physiology, 2007, Vol 211, Issue 1, p36
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.20897