Konfino Tal, Landa Natalie, Ben-Mordechai Tammy, Leor Jonathan
Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, Israel (T.K., N.L., T.B.M., J.L.) Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel (T.K., N.L., T.B.M., J.L.) Sheba Center for Regenerative Medicine, Stem Cells and Tissue Engineering, Tel-Hashomer, Israel (T.K., N.L., T.B.M., J.L.).
J Am Heart Assoc. 2015 Jan 27;4(1):e001320. doi: 10.1161/JAHA.114.001320.
The neonatal heart possesses the unique power to regenerate in response to resection of the left ventricular apex. We sought to determine whether the type of injury affects the mode of repair and regeneration.
Apical resection, or permanent left anterior descending coronary artery ligation, was induced in neonatal 1-day-old mice. Echocardiography was used to confirm and monitor cardiac injury and remodeling. Histological and immunohistochemical examinations of the resected and infarcted neonatal hearts revealed inflammation and granulation tissue formation. From day 3, early regeneration was identified at the injured sites and was characterized by dedifferentiation and proliferation of cardiomyocytes around the injured areas. The young cardiomyocytes infiltrated the granulation tissue and replaced it with a new myocardium. The ability of neonatal cardiomyocytes to proliferate was confirmed in neonatal heart organ cultures. Notably, myocardial infarction in neonatal mouse produced incomplete regeneration with a residual small infarct and, sometimes, aneurysm at 28 days after myocardial infarction. We then repeated the same experiments in the adult heart. Remarkably, myocardial infarction in the adult mouse heart produced a typical thin scar, whereas apical resection revealed an abnormal, epicardial, hemorrhagic scar 21 days after injury.
Our findings suggest that the type of injury, resection, or infarction affects the mode of repair in both neonatal and adult mouse hearts. Identifying the differences in the mechanisms or repair of these 2 types of injuries could help to develop novel regenerative therapies relevant to human patients.
新生小鼠心脏具有独特的能力，可对左心室心尖切除作出再生反应。我们试图确定损伤类型是否会影响修复和再生模式。
对出生1天的新生小鼠进行心尖切除或永久性左前降支冠状动脉结扎。采用超声心动图确认并监测心脏损伤及重塑情况。对切除和梗死的新生心脏进行组织学和免疫组织化学检查，结果显示有炎症和肉芽组织形成。从第3天开始，在损伤部位发现早期再生，其特征为损伤区域周围的心肌细胞去分化和增殖。年轻的心肌细胞浸润肉芽组织，并用新的心肌组织取代它。在新生心脏器官培养中证实了新生心肌细胞的增殖能力。值得注意的是，新生小鼠心肌梗死后28天会产生不完全再生，伴有残留的小梗死灶，有时还会出现动脉瘤。然后我们在成年心脏中重复相同的实验。值得注意的是，成年小鼠心脏心肌梗死后会产生典型的薄瘢痕，而心尖切除术后21天会出现异常的心外膜出血性瘢痕。
我们的研究结果表明，损伤类型（切除或梗死）会影响新生和成年小鼠心脏的修复模式。明确这两种损伤修复机制的差异可能有助于开发与人类患者相关的新型再生疗法。
