Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats.
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.
Shibata
Taiga
T
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Naruse
Keiko
K
Kamiya
Hideki
H
Kozakae
Mika
M
Kondo
Masaki
M
Yasuda
Yutaka
Y
Nakamura
Nobuhisa
N
Ota
Kimiko
K
Tosaki
Takahiro
T
Matsuki
Takashi
T
Nakashima
Eitaro
E
Hamada
Yoji
Y
Oiso
Yutaka
Y
Nakamura
Jiro
J
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
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