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: Yong Sook Kim, Youngkeun Ahn, Jin Sook Kwon, Young Kuk Cho, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang
• Journal: Cells, tissues, organs (Cells Tissues Organs) Vol. 195 Issue 5 Pg. 428-42 ( 2012) ISSN: 1422-6421 [Electronic] Switzerland
• PMID: 21893931 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Oxytocin

Topics

• Animals
• Cord Blood Stem Cell Transplantation
• Fetal Blood (cytology, drug effects)
• Humans
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, drug effects, pathology)
• Myocardial Reperfusion Injury (drug therapy, pathology, surgery)
• Myocytes, Cardiac (drug effects, pathology)
• Oxytocin (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Wound Healing (drug effects)