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.

Nonsocial Functions of Hypothalamic Oxytocin

“…OXT also has a promigratory effect on umbilical cord blood-derived mesenchymal stem cells [36]. Prolonged treatment of these cells with OXT can significantly increase the expression of connexin 43, cardiac troponin I, and alpha-sarcomeric actin when they are cocultured with cardiomyocytes [37]. Thus, OXT is potentially useful to advance embryonic stem cell development to reverse osteoporosis and repair infarction damaged cardiac tissue.…”

Preconditioning of Stem Cells by Oxytocin to Improve Their Therapeutic Potential

“…Such results could have important consequences for cellular therapy applications, because OT-primed cells may play a supportive role by optimizing host vasculature milieu and promote healing by altering cell response to ischemia. Recently, Kim et al (10) reported the priming of human MSC with OT to enhance the cardiac repair in a rat model of ischemia/reperfusion injury. In this latter study, OT-treated MSC expressed cardiac markers, and when transplanted into rat ischemic heart, MSC reduced fibrosis and improved cardiac functional recovery.…”

Placenta-based therapies for the treatment of epidermolysis bullosa

“…On day 8, average relative wound closure for UCB, BM and PB MSC treated wounds was significantly different at 58%, 42%, and 22%, respectively. Based on a histological analysis, the authors also noted that both granulation tissue and re-epithelialization of UCB MSC-treated wounds appeared to be thicker and larger than those treated with BM or PB MSCs [36]. Cumulatively, these studies (summarized in Table 2) provide evidence to support the use of MSC-based therapies for the treatment of RDEB and, although less definitively, suggest that UCB MSCs may have an advantage over MSCs isolated from other tissues.…”