title: Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats.
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.
  
  
  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.
authors: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Taiga
authors: T
authors: Shibata
authors: Keiko
authors: K
authors: Naruse
authors: Hideki
authors: H
authors: Kamiya
authors: Mika
authors: M
authors: Kozakae
authors: Masaki
authors: M
authors: Kondo
authors: Yutaka
authors: Y
authors: Yasuda
authors: Nobuhisa
authors: N
authors: Nakamura
authors: Kimiko
authors: K
authors: Ota
authors: Takahiro
authors: T
authors: Tosaki
authors: Takashi
authors: T
authors: Matsuki
authors: Eitaro
authors: E
authors: Nakashima
authors: Yoji
authors: Y
authors: Hamada
authors: Yutaka
authors: Y
authors: Oiso
authors: Jiro
authors: J
authors: Nakamura
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C518911:neurotropin 3, mouse; D016222:Fibroblast Growth Factor 2; D020932:Nerve Growth Factor