Transplantation of Bone Marrow–Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats

  1. Taiga Shibata1,
  2. Keiko Naruse12,
  3. Hideki Kamiya1,
  4. Mika Kozakae1,
  5. Masaki Kondo1,
  6. Yutaka Yasuda1,
  7. Nobuhisa Nakamura1,
  8. Kimiko Ota1,
  9. Takahiro Tosaki1,
  10. Takashi Matsuki1,
  11. Eitaro Nakashima1,
  12. Yoji Hamada3,
  13. Yutaka Oiso1 and
  14. Jiro Nakamura1
  1. 1Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan
  2. 2Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
  3. 3Department of Metabolic Medicine, Nagoya University School of Medicine, Nagoya, Japan
  1. Corresponding author: Jiro Nakamura, jiro{at}med.nagoya-u.ac.jp

Abstract

OBJECTIVE—Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neurosupportive 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 hind limb skeletal muscles of rats with an 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), sciatic nerve blood flow (SNBF), capillary number–to–muscle fiber ratio in soleus muscles, and sural nerve morphometry were evaluated.

RESULTS—VEGF and bFGF mRNA expression were significantly increased in MSC-injected thigh muscles of STZ-induced diabetic rats. Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted sites was confirmed. STZ-induced 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 STZ-induced 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.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 26 August 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted August 14, 2008.
    • Received January 9, 2008.
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  1. Diabetes vol. 57 no. 11 3099-3107
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