Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.
Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34-, and CD45-) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce cerebral infarction volume and improve functional outcome.
Honma
T
T
Department of Neurosurgery, Sapporo Medical University School of Medicine, South-1st, West-16th, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
Honmou
O
O
Iihoshi
S
S
Harada
K
K
Houkin
K
K
Hamada
H
H
Kocsis
J D
JD
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005080:Exercise Test / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007262:Infusions, Intravenous / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015703:Antigens, CD; D049452:Green Fluorescent Proteins; D010751:Phosphopyruvate Hydratase