title: Attenuation of Postischemic Genomic Alteration by Mesenchymal Stem Cells: a Microarray Study.
abstract: Intravenous administration of mesenchymal stem cells (IV-MSC) protects the ischemic rat brain in a stroke model, but the molecular mechanism underlying its therapeutic effect is unclear. We compared genomic profiles using the mRNA microarray technique in a rodent stroke model. Rats were treated with 1 × 10(6) IV-MSC or saline (sham group) 2 h after transient middle cerebral artery occlusion (MCAo). mRNA microarray was conducted 72 h after MCAo using brain tissue from normal rats (normal group) and the sham and MSC groups. Predicted pathway analysis was performed in differentially expressed genes (DEGs), and functional tests and immunohistochemistry for inflammation-related proteins were performed. We identified 857 DEGs between the sham and normal groups, with the majority of them (88.7%) upregulated in sham group. Predicted pathway analysis revealed that cerebral ischemia activated 10 signaling pathways mainly related to inflammation and cell cycle. IV-MSC attenuated the numbers of dysregulated genes in cerebral ischemia (118 DEGs between the MSC and normal groups). In addition, a total of 218 transcripts were differentially expressed between the MSC and sham groups, and most of them (175/218 DEGs, 80.2%) were downregulated in the MSC group. IV-MSC reduced the number of Iba-1(+) cells in the peri-infarct area, reduced the overall infarct size, and improved functional deficits in MCAo rats. In conclusion, transcriptome analysis revealed that IV-MSC attenuated postischemic genomic alterations in the ischemic brain. Amelioration of dysregulated inflammation- and cell cycle-related gene expression in the host brain is one of the molecular mechanisms of IV-MSC therapy for cerebral ischemia.
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam 463-400, Korea.
authors.forename: Chunggab
authors.initials: C
authors.lastname: Choi
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 463-712, Korea.
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam 463-400, Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Noh
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam 463-400, Korea.
authors.forename: Yong-Woo
authors.initials: YW
authors.lastname: Jeong
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung 25601, Korea.|Catholic Kwandong University International St. Mary's Hospital, Incheon 22711, Korea.
authors.forename: Soonhag
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam 463-400, Korea.
authors.forename: Jung Jae
authors.initials: JJ
authors.lastname: Ko
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 463-712, Korea.
authors.forename: Ok-Joon
authors.initials: OJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam 463-400, Korea.|CHA Stem Cell Institute, CHA University, Seongnam 463-400, Korea.
authors.forename: Jihwan
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000628:therapy*; D002453:Cell Cycle; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D051381:Rats; D015398:Signal Transduction; D020521:Stroke / Q000235:genetics / Q000517:prevention & control*
keywords: inflammation; mesenchymal stem cells; microarray; stroke; transcriptome