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BioMed Research International
Volume 2013, Article ID 259187, 12 pages
Research Article

Mesenchymal Stem Cell-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Ameliorate Diabetic Polyneuropathy in Mice

1Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan
2Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan
3Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan
4Department of CKD Initiatives, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan
5Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8651, Japan
6Department of Metabolic Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan

Received 31 July 2013; Accepted 11 September 2013

Academic Editor: Ji Wu

Copyright © 2013 Tatsuhito Himeno et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Although pathological involvements of diabetic polyneuropathy (DPN) have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated. Results. The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100β in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice. Conclusions. These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.