Am J Stem Cell 2012;1(2):128-137

Original Article
Reprogramming of bone marrow-derived mesenchymal stem cells into functional
insulin-producing cells by chemical regimen

Qiwei Wang, Lingling Ye, Hong Liu, Xingmao Liu, Shichong Li, Zhaolie Chen

Department of Cell Engineering, Beijing Institute of Biotechnology, 20 Dongda Street, Fengtai District, Beijing 100071, P. R. China

Received January 11, 2012; accepted January 30, 2012; Epub March 28, 2012; Published June 30, 2012

Abstract: Beta-cell transplantation is considered to be the most effective approach to cure type 1 diabetes (T1D). Unfortunately, the
scarce availability of donor tissue limits the applicability of this therapy. Recent stem cell research progress shows stem cell therapy may
be a potential means to solve this problem. Bone marrow-derived mesenchymal stem cells (MSCs) are self-renewable and multipotent
adult stem cells which can differentiate into the three germ layers. Here we aimed to investigate whether MSCs could be reprogrammed
into insulin-producing cells (IPCs). We isolated and characterized MSCs obtained from rat bone marrow. Then MSCs were induced to
transdifferentiate into IPCs under specific conditions containing high concentrations of glucose, activin A, all-trans retinoic acid, and other
maturation factors. The induced cells expressed multiple genes related to pancreatic beta-cell development and function, such as
insulin1, glucagon, Pdx1, Pax6, and Glut-2. Insulin1 and C-peptide production were identified by immunocytochemistry. In vitro glucose
challenge studies showed the induced cells secreted insulin in a glucose-dependent manner, as do normal pancreatic beta-cells.
Transplantation of these MSC-derived insulin-positive cells could reverse the hyperglycemia of streptozotcin (STZ)-induced diabetic rats.
These results demonstrated that MSCs could be reprogrammed into IPCs and might be a potential autologous cell source for
transplantation therapy of T1D. (AJSC1201002).

Keywords: Reprogramming, bone marrow, mesenchymal stem cells, insulin-producing cells

Address all correspondence to:
Dr. Qiwei Wang
Department of Cell Engineering
Beijing Institute of Biotechnology
20 Dongda Street, Fengtai District
Beijing 100071, P. R. China.
Tel: +86-10-63841526; Fax: +86-10-63841526
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