RRC ID 28687
Author Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, Kato K, Honmou O, Houkin K, Date I, Hamada H.
Title BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model.
Journal Mol. Ther.
Abstract 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.
Volume 9(2)
Pages 189-97
Published 2004-2
DOI 10.1016/j.ymthe.2003.10.012
PII S1525-0016(03)00354-X
PMID 14759803
MeSH Adenoviridae / genetics Animals Brain-Derived Neurotrophic Factor / genetics* Brain-Derived Neurotrophic Factor / immunology Brain-Derived Neurotrophic Factor / metabolism Brain-Derived Neurotrophic Factor / therapeutic use* DNA Fragmentation Disease Models, Animal* Genetic Therapy* Genetic Vectors / genetics Humans Infarction, Middle Cerebral Artery / genetics Infarction, Middle Cerebral Artery / pathology* Infarction, Middle Cerebral Artery / therapy* Magnetic Resonance Imaging Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells / cytology Mesenchymal Stromal Cells / immunology Mesenchymal Stromal Cells / metabolism* Phenotype Rats
IF 7.008
Times Cited 207
DNA material pWEAxCAhBDNF-F/RGD (RDB03974) AxCAhBDNF-F/RGD (RDB03975) pCAhBDNF (RDB03981).