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

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.

• Authors: 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
• Journal: Journal of diabetes investigation (J Diabetes Investig) Vol. 6 Issue 2 Pg. 140-9 (Mar 2015) ISSN: 2040-1116 [Print] Japan
• PMID: 25802721 (Publication Type: Journal Article)