Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.
Mesenchymal stem cells (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 previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.
Kurozumi
Kazuhiko
K
Department of Molecular Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
Nakamura
Kiminori
K
Tamiya
Takashi
T
Kawano
Yutaka
Y
Ishii
Keiji
K
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
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004801:Eosine Yellowish-(YS); D015316:Genetic Therapy; D006416:Hematoxylin; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013778:Tetrazolium Salts / Q000494:pharmacology
D009414:Nerve Growth Factors; D013778:Tetrazolium Salts; C003110:phenyltetrazolium; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin