title: Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kurozumi
authors.forename: Kiminori
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamiya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawano
authors.forename: Keiji
authors.initials: K
authors.lastname: Ishii
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.forename: Sachie
authors.initials: S
authors.lastname: Hirai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Uchida
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kato
authors.forename: Osamu
authors.initials: O
authors.lastname: Honmou
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
authors.forename: Isao
authors.initials: I
authors.lastname: Date
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
mesh_terms: 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
chemical_list: D009414:Nerve Growth Factors; D013778:Tetrazolium Salts; C003110:phenyltetrazolium; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin