title: Priming of mesenchymal stem cells with oxytocin enhances the cardiac repair in ischemia/reperfusion injury.
abstract: Oxytocin stimulates the cardiomyogenesis of embryonic stem cells and adult cardiac stem cells. We previously reported that oxytocin has a promigratory effect on umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). In this study, UCB-MSCs were cultured with oxytocin and examined for their therapeutic effect in an infarcted heart. UCB-MSCs were pretreated with 100 nM oxytocin and cardiac markers were assessed by immunofluorescence staining. Next, oxytocin-supplemented USC-MSCs (OT-USCs) were cocultured with hypoxia/reoxygenated neonatal rat cardiomyocytes and cardiac markers and dye transfer were then examined. For the in vivo study, ischemia/reperfusion was induced in rats, and phosphate-buffered saline (group 1), 1-day OT-USCs (group 2), or 7-day OT-USCs (group 3) were injected into the infarcted myocardium. Two weeks after injection, histological changes and cardiac function were examined. UCB-MSCs expressed connexin 43 (Cnx43), cardiac troponin I (cTnI), and α-sarcomeric actin (α-SA) after oxytocin supplementation and coculture with cardiomyocytes. Functional gap junction formation was greater in group 3 than in groups 1 and 2. Cardiac fibrosis and macrophage infiltration were lower in group 3 than in group 2. Restoration of Cnx43 expression was greater in group 3 than in group 2. Cnx43- and cTnI-positive OT-USCs in the peri-infarct zone were observed in group 2 and more frequently in group 3. The ejection fraction (EF) was increased in groups 2 and 3 in 2 weeks. The improved EF was sustained for 4 weeks only in group 3. Our findings suggest that the supplementation of UCB-MSCs with oxytocin can contribute to the cardiogenic potential for cardiac repair.
authors: Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.
authors: Yong Sook
authors: YS
authors: Kim
authors: Youngkeun
authors: Y
authors: Ahn
authors: Jin Sook
authors: JS
authors: Kwon
authors: Young Kuk
authors: YK
authors: Cho
authors: Myung Ho
authors: MH
authors: Jeong
authors: Jeong Gwan
authors: JG
authors: Cho
authors: Jong Chun
authors: JC
authors: Park
authors: Jung Chaee
authors: JC
authors: Kang
mesh_terms: D000818:Animals; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D010121:Oxytocin