RRC ID 28674
Author Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Ishii K, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, Kato K, Honmou O, Houkin K, Date I, Hamada H.
Title Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.
Journal Mol. Ther.
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.
Volume 11(1)
Pages 96-104
Published 2005-1
DOI 10.1016/j.ymthe.2004.09.020
PII S1525-0016(04)01474-1
PMID 15585410
MeSH Animals Brain Ischemia / genetics Brain Ischemia / metabolism* Brain Ischemia / pathology* Brain Ischemia / therapy Cells, Cultured Disease Models, Animal Eosine Yellowish-(YS) Genetic Therapy Hematoxylin Humans Infarction, Middle Cerebral Artery / genetics Infarction, Middle Cerebral Artery / metabolism* Infarction, Middle Cerebral Artery / pathology* Infarction, Middle Cerebral Artery / therapy Male Mesenchymal Stromal Cells / metabolism* Nerve Growth Factors / administration & dosage Nerve Growth Factors / genetics* Nerve Growth Factors / metabolism* Rats Rats, Wistar Staining and Labeling Tetrazolium Salts / pharmacology
IF 7.008
Times Cited 242
DNA material pWEAxCAhBDNF-F/RGD (RDB03974) AxCAhBDNF-F/RGD (RDB03975) pCAhGDNF (RDB03976) pWEAxCAhGDNF-F/RGD (RDB03977) AxCAhGDNF-F/RGD (RDB03978) pCAhBDNF (RDB03981)