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Kondo M, Kamiya H, Himeno T, et al. Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes. J Diabetes Investig. 2014;6(2):140-9doi: 10.1111/jdi.12272.
Kondo, M., Kamiya, H., Himeno, T., Naruse, K., Nakashima, E., Watarai, A., Shibata, T., Tosaki, T., Kato, J., Okawa, T., Hamada, Y., Isobe, K., Oiso, Y., & Nakamura, J. (2015). Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes. Journal of diabetes investigation, 6(2), 140-9. https://doi.org/10.1111/jdi.12272
Kondo, Masaki, et al. "Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes." Journal of diabetes investigation vol. 6,2 (2015): 140-9. doi: https://doi.org/10.1111/jdi.12272
Kondo M, Kamiya H, Himeno T, Naruse K, Nakashima E, Watarai A, Shibata T, Tosaki T, Kato J, Okawa T, Hamada Y, Isobe K, Oiso Y, Nakamura J. Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes. J Diabetes Investig. 2015 Mar;6(2):140-9. doi: 10.1111/jdi.12272. Epub 2014 Sep 11. PMID: 25802721; PMCID: PMC4364848.
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J Diabetes Investig. 2015 Mar;6(2):140-9. doi: 10.1111/jdi.12272. Epub 2014 Sep 11.

Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes.

Journal of diabetes investigation

Masaki Kondo, Hideki Kamiya, Tatsuhito Himeno, Keiko Naruse, Eitaro Nakashima, Atsuko Watarai, Taiga Shibata, Takahiro Tosaki, Jiro Kato, Tetsuji Okawa, Yoji Hamada, Ken-Ichi Isobe, Yutaka Oiso, Jiro Nakamura

Affiliations

  1. Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan ; Department of Immunology, Nagoya University Graduate School of Medicine Nagoya, Japan.
  2. Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan ; Department of CKD Initiatives, Nagoya University Graduate School of Medicine Nagoya, Japan.
  3. Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
  4. Department of Metabolic Medicine, Nagoya University Graduate School of Medicine Nagoya, Japan.
  5. Department of Immunology, Nagoya University Graduate School of Medicine Nagoya, Japan.

PMID: 25802721 PMCID: PMC4364848 DOI: 10.1111/jdi.12272

Abstract

AIMS/INTRODUCTION: Recent studies have shown that cell transplantation therapies, such as endothelial precursor cells, bone marrow-derived mononuclear cells (BM-MNCs) and mesenchymal stem cells, are effective on diabetic polyneuropathy through ameliorating impaired nerve blood flow in diabetic rats. Here, we investigated the effects of BM-MNCs transplantation in diabetic polyneuropathy using BM-MNCs derived from adult (16-week-old) diabetic (AD), adult non-diabetic (AN) or young (8-week-old) non-diabetic (YN) rats.

MATERIALS AND METHODS: BM-MNCs of AD and AN were isolated after an 8-week diabetes duration. The BM-MNCs were characterized using flow cytometry analysis of cell surface markers and reverse transcription polymerase chain reaction of several cytokines. BM-MNCs or saline were injected into hind limb muscles. Four weeks later, the thermal plantar test, nerve conduction velocity, blood flow of the sciatic nerve and capillary-to-muscle fiber ratio were evaluated.

RESULTS: The number of CD29(+)/CD90(+) cells that host mesenchymal stem cells in BM-MNCs decreased in AD compared with AN or YN, and transcript expressions of basic fibroblast growth factor and nerve growth factor in BM-MNCs decreased in AD compared with AN or YN. Impaired thermal sensation, decreased blood flow of the sciatic nerve and delayed nerve conduction velocity in 8-week-diabetic rats were significantly ameliorated by BM-MNCs derived from YN, whereas BM-MNCs from AD or AN rats did not show any beneficial effect in these functional tests.

CONCLUSIONS: These results show that cytokine production abilities and the mesenchymal stem cell population of BM-MNCs would be modified by aging and metabolic changes in diabetes, and that these differences could explain the disparity of the therapeutic efficacy of BM-MNCs between young and adult or diabetic and non-diabetic patients in diabetic polyneuropathy.

Keywords: Aging; Diabetic polyneuropathy; Neurotrophic factors

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