Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model.
Previous studies have suggested that intravenous transplantation of mesenchymal stem cells (MSCs) in rat ischemia models reduces ischemia-induced brain damage. Here, we analyzed the expression of neurotrophic factors in transplanted human MSCs and host brain tissue in rat middle cerebral artery occlusion (MCAO) ischemia model. At 1 day after transient MCAO, 3 x 10(6) immortalized human MSC line (B10) cells or PBS was intravenously transplanted. Behavioral tests, infarction volume, and B10 cell migration were investigated at 1, 3, 7, and 14 days after MCAO. The expression of endogenous (rat origin) and exogenous (human origin) neurotrophic factors and cytokines was evaluated by quantitative real-time RT-PCR and Western blot analysis. Compared with PBS controls, rats receiving MSC transplantation showed improved functional recovery and reduced brain infarction volume at 7 and 14 days after MCAO. In MSC-transplanted brain, among many neurotrophic factors, only human insulin-like growth factor 1 (IGF-1) was detected in the core and ischemic border zone at 3 days after MCAO, whereas host cells expressed markedly higher neurotrophic factors (rat origin) than control rats, especially vascular endothelial growth factor (VEGF) at 3 days and epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) at 7 days after MCAO. Intravenously transplanted human MSCs induced functional improvement, reduced infarct volume, and neuroprotection in ischemic rats, possibly by providing IGF-1 and inducing VEGF, EGF, and bFGF neurotrophic factors in host brain.
Wakabayashi
Kiryo
K
Department of Neurology, Shimane University School of Medicine, Izumo, Japan.
Nagai
Atsushi
A
Sheikh
Abdullah Md
AM
Shiota
Yuri
Y
Narantuya
Dashdemberel
D
Watanabe
Tatsuzo
T
Masuda
Junichi
J
Kobayashi
Shotai
S
Kim
Seung U
SU
Yamaguchi
Shuhei
S
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism* / Q000628:therapy*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004185:Disability Evaluation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000628:therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D012038:Regeneration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D001973:Bromodeoxyuridine