title: Mesenchymal stem cells expressing brain-derived neurotrophic factor enhance endogenous neurogenesis in an ischemic stroke model.
abstract: Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2'-deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.
authors.affiliation: Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Jeong
authors.affiliation: Postech-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Seong Muk
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Postech-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Chung Heon
authors.initials: CH
authors.lastname: Ryu
authors.affiliation: Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Jin Ae
authors.initials: JA
authors.lastname: Jun
authors.affiliation: Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea ; Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Sin-Soo
authors.initials: SS
authors.lastname: Jeun
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D055495:Neurogenesis; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein