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 |
2005-1-1
|
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 Stem 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 |
8.986
|
Times Cited |
300
|
WOS Category
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
MEDICINE, RESEARCH & EXPERIMENTAL
|
Resource |
DNA material |
pWEAxCAhBDNF-F/RGD (RDB03974)
AxCAhBDNF-F/RGD (RDB03975)
pCAhGDNF (RDB03976)
pWEAxCAhGDNF-F/RGD (RDB03977)
AxCAhGDNF-F/RGD (RDB03978)
pCAhBDNF (RDB03981) |