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Diabetes Publish Ahead of Print published online ahead of print August 26, 2008
DOI: 10.2337/db08-0031
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Original Research

Transplantation of Bone Marrow-derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats.

Taiga Shibata1, Keiko Naruse1,2, Hideki Kamiya1, Mika Kozakae1, Masaki Kondo1, Yutaka Yasuda1, Nobuhisa Nakamura1, Kimiko Ota1, Takahiro Tosaki1, Takashi Matsuki1, Eitaro Nakashima1, Yoji Hamada3, Yutaka Oiso1, and Jiro Nakamura1

1Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan
2Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
3Department of Metabolic Medicine, Nagoya University School of Medicine, Nagoya, Japan

Objective: Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neuro-supportive effects. This study was conducted to investigate the effects of MSC transplantation on diabetic polyneuropathy (DPN) in rats.

Research Design and Methods: MSCs were isolated from bone marrow of adult rats, and transplanted into hindlimb skeletal muscles of rats with 8-week duration of streptozotocin (STZ)–induced diabetes or age-matched normal rats by unilateral intramuscular injection. Four weeks after transplantation, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) productions in transplanted sites, current perception threshold, nerve conduction velocity (NCV), nerve blood flow of sciatic nerves (SNBF), capillary number to muscle fiber ratio in soleus muscles and sural nerve morphometry were evaluated.

Results: VEGF and bFGF mRNA expression was significantly increased in MSCs-injected thigh muscles of diabetic rats. Furthermore, co-localization of MSCs with VEGF and bFGF in the transplanted sites was confirmed. Diabetic rats showed hypoalgesia, delayed NCV, decreased SNBF and decreased capillary number to muscle fiber ratio in soleus muscles, which were all ameliorated by MSC transplantation. Sural nerve morphometry showed decreased axonal circularity in diabetic rats, which was normalized by MSC transplantation.

Conclusions: These results suggest that MSC transplantation could have therapeutic effects on DPN through paracrine actions of growth factors secreted by MSCs.

Correspondence: jiro{at}med.nagoya-u.ac.jp


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Copyright © 2008 by the American Diabetes Association.