title: Promigratory activity of oxytocin on umbilical cord blood-derived mesenchymal stem cells.
abstract: Recent studies show that oxytocin has various effects on cellular behaviors. Oxytocin is reported to stimulate cardiomyogenesis of embryonic stem cells and endothelial cell proliferation. Mesenchymal stem cells (MSCs) are widely used for cardiac repair, and we elucidated the effect of oxytocin on umbilical cord derived-MSCs (UCB-MSCs). UCB-MSCs were pretreated with oxytocin (100 nM) and washed with saline prior to experiments. To evaluate their angiogenic potential and migration activity, tube formation assay and Boyden chamber assay were performed. For in vivo study, ischemia-reperfusion was induced in rats, and UCB-MSCs with or without oxytocin pretreatment were injected into the infarcted myocardium to evaluate the engraftment of injected cells. Histological and hemodynamic studies were performed. Oxytocin-treated UCB-MSCs showed a decrease in tube formation but a drastic increase in transwell migration activity. The transcription level of matrix metalloproteinase (MMP)-2 was increased in oxytocin-treated UCB-MSCs. Knock-down of MMP-2 by use of siRNA restored the tube formation, while reducing transmigration activity. In rats injected with oxytocin-treated UCB-MSCs, cardiac fibrosis and CD68 infiltration in the peri-infarct zone were reduced, whereas cell engraftment and connexin43 expression were greater than in rats injected with untreated UCB-MSCs. By contrast, angiogenesis did not differ significantly between the two groups. Cardiac contractility was higher in the group injected with oxytocin-treated UCB-MSCs than in the group injected with phosphate-buffered saline alone. Collectively, oxytocin is an effective priming reagent for stem cells for application to damaged heart tissue.
authors.affiliation: The Heart Center of Chonnam National University Hospital, 8 Hak Dong, Dong Ku, Gwangju 501-757, South Korea.
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kwon
authors.forename: Moon Hwa
authors.initials: MH
authors.lastname: Hong
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Song
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Jeong Gwan
authors.initials: JG
authors.lastname: Cho
authors.forename: Jong Chun
authors.initials: JC
authors.lastname: Park
authors.forename: Jung Chae
authors.initials: JC
authors.lastname: Kang
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D055785:Gene Knockdown Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010121:Oxytocin / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000628:therapy*
chemical_list: D034741:RNA, Small Interfering; D010121:Oxytocin; D020778:Matrix Metalloproteinase 2