BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model.
Examination of the clinical therapeutic efficacy of using bone marrow stromal cells, including mesenchymal stem cells (MSC), has recently been the focus of much investigation. MSC were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we transfected telomerized human MSC with the BDNF gene using a fiber-mutant F/RGD adenovirus vector and investigated whether these cells contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. BDNF production by MSC-BDNF cells was 23-fold greater than that seen in uninfected MSC. Rats that received MSC-BDNF showed significantly more functional recovery than did control rats following MCAO. Specifically, MRI analysis revealed that the rats in the MSC-BDNF group exhibited more significant recovery from ischemia after 7 and 14 days. The number of TUNEL-positive cells in the ischemic boundary zone was significantly smaller in animals treated with MSC-BDNF compared to animals in the control group. These data suggest that MSC transfected with the BDNF gene may be useful in the treatment of cerebral ischemia and may represent a new strategy for the treatment of stroke.
Kurozumi
Kazuhiko
K
Department of Molecular Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Nakamura
Kiminori
K
Tamiya
Takashi
T
Kawano
Yutaka
Y
Kobune
Masayoshi
M
Hirai
Sachie
S
Uchida
Hiroaki
H
Sasaki
Katsunori
K
Ito
Yoshinori
Y
Kato
Kazunori
K
Honmou
Osamu
O
Houkin
Kiyohiro
K
Date
Isao
I
Hamada
Hirofumi
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor