title: Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes.
abstract: OBJECTIVE
  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.
  
  
  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: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan ; Department of Immunology, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Masaki
authors: M
authors: Kondo
authors: 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.
authors: Hideki
authors: H
authors: Kamiya
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Tatsuhito
authors: T
authors: Himeno
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Keiko
authors: K
authors: Naruse
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Eitaro
authors: E
authors: Nakashima
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Atsuko
authors: A
authors: Watarai
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Taiga
authors: T
authors: Shibata
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Takahiro
authors: T
authors: Tosaki
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Jiro
authors: J
authors: Kato
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Tetsuji
authors: T
authors: Okawa
authors: Department of Metabolic Medicine, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Yoji
authors: Y
authors: Hamada
authors: Department of Immunology, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Ken-Ichi
authors: K
authors: Isobe
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Yutaka
authors: Y
authors: Oiso
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors: Jiro
authors: J
authors: Nakamura
keywords: Aging; Diabetic polyneuropathy; Neurotrophic factors