PMID- 24672780 OWN - NLM STAT- MEDLINE DCOM- 20150513 LR - 20211203 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2014 DP - 2014 TI - Mesenchymal stem cells expressing brain-derived neurotrophic factor enhance endogenous neurogenesis in an ischemic stroke model. PG - 129145 LID - 10.1155/2014/129145 [doi] LID - 129145 AB - 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. FAU - Jeong, Chang Hyun AU - Jeong CH AD - Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea. FAU - Kim, Seong Muk AU - Kim SM AD - Postech-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 137-701, Republic of Korea. FAU - Lim, Jung Yeon AU - Lim JY AD - Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea. FAU - Ryu, Chung Heon AU - Ryu CH AD - Postech-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 137-701, Republic of Korea. FAU - Jun, Jin Ae AU - Jun JA AD - Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea. FAU - Jeun, Sin-Soo AU - Jeun SS AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140205 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dcx protein, rat) RN - 0 (Doublecortin Protein) SB - IM MH - Adult MH - Animals MH - Apoptosis MH - Brain Ischemia/complications/physiopathology/*therapy MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cells, Cultured MH - Disease Models, Animal MH - Doublecortin Protein MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - In Situ Nick-End Labeling MH - Infarction, Middle Cerebral Artery/complications/physiopathology/therapy MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Middle Aged MH - *Neurogenesis MH - Rats, Sprague-Dawley MH - Stroke/complications/physiopathology/*therapy MH - Young Adult PMC - PMC3933216 EDAT- 2014/03/29 06:00 MHDA- 2015/05/15 06:00 PMCR- 2014/02/05 CRDT- 2014/03/28 06:00 PHST- 2013/09/24 00:00 [received] PHST- 2013/12/29 00:00 [accepted] PHST- 2014/03/28 06:00 [entrez] PHST- 2014/03/29 06:00 [pubmed] PHST- 2015/05/15 06:00 [medline] PHST- 2014/02/05 00:00 [pmc-release] AID - 10.1155/2014/129145 [doi] PST - ppublish SO - Biomed Res Int. 2014;2014:129145. doi: 10.1155/2014/129145. Epub 2014 Feb 5.