Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.
Cells Tissues Organs. 2012;195(5):428-42. doi: 10.1159/000329234. Epub 2011 Aug 31.
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.
催产素可刺激胚胎干细胞和成人心脏干细胞的心肌生成。我们之前曾报道，催产素对脐带血源性间充质干细胞（UCB-MSCs）具有促迁移作用。在本研究中，我们用催产素培养 UCB-MSCs，观察其在梗死心脏中的治疗效果。用 100 nM 催产素预处理 UCB-MSCs，通过免疫荧光染色评估其心脏标志物。接着，将补充了催产素的 UCB-MSCs（OT-USCs）与缺氧/复氧新生大鼠心肌细胞共培养，然后检测心脏标志物和染料转移。在体内研究中，诱导大鼠发生缺血/再灌注，将磷酸盐缓冲液（第 1 组）、1 天 OT-USCs（第 2 组）或 7 天 OT-USCs（第 3 组）注入梗死心肌。注射后 2 周，检查组织学变化和心功能。UCB-MSCs 在补充催产素并与心肌细胞共培养后表达连接蛋白 43（Cnx43）、心肌肌钙蛋白 I（cTnI）和α-横纹肌肌动蛋白（α-SA）。第 3 组的功能性缝隙连接形成比第 1 组和第 2 组更大。第 3 组的心肌纤维化和巨噬细胞浸润比第 2 组更低。第 3 组的 Cnx43 表达恢复比第 2 组更大。第 2 组和第 3 组的梗死周边区可见 Cnx43 和 cTnI 阳性的 OT-USCs，第 3 组更常见。2 周时，第 2 组和第 3 组的射血分数（EF）增加。仅在第 3 组中，改善的 EF 持续了 4 周。我们的研究结果表明，用催产素补充 UCB-MSCs 有助于提高心脏修复的心脏生成潜力。
