Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Winsloewparken 21 , 5000 Odense C, Denmark ; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark.
Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Winsloewparken 21 , 5000 Odense C, Denmark ; Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark.
Stem Cell Reports. 2014 Apr 3;2(4):406-13. doi: 10.1016/j.stemcr.2014.02.008. eCollection 2014 Apr 8.
The mammalian heart has generally been considered nonregenerative, but recent progress suggests that neonatal mouse hearts have a genuine capacity to regenerate following apex resection (AR). However, in this study, we performed AR or sham surgery on 400 neonatal mice from inbred and outbred strains and found no evidence of complete regeneration. Ideally, new functional cardiomyocytes, endothelial cells, and vascular smooth muscle cells should be formed in the necrotic area of the damaged heart. Here, damaged hearts were 9.8% shorter and weighed 14% less than sham controls. In addition, the resection border contained a massive fibrotic scar mainly composed of nonmyocytes and collagen disposition. Furthermore, there was a substantial reduction in the number of proliferating cardiomyocytes in AR hearts. Our results thus question the usefulness of the AR model for identifying molecular mechanisms underlying regeneration of the adult heart after damage.
哺乳动物的心脏通常被认为是不可再生的,但最近的进展表明,新生小鼠的心脏在切除心尖(apex resection,AR)后确实具有真正的再生能力。然而,在这项研究中,我们对来自近交系和远交系的 400 只新生小鼠进行了 AR 或假手术,没有发现完全再生的证据。理想情况下,坏死区应形成新的功能性心肌细胞、内皮细胞和血管平滑肌细胞。这里,受损心脏比假手术对照组短 9.8%,重量轻 14%。此外,切除边界包含一个主要由非心肌细胞和胶原蛋白组成的大量纤维瘢痕。此外,AR 心脏中增殖的心肌细胞数量显著减少。因此,我们的结果质疑了 AR 模型在识别损伤后成年心脏再生的分子机制方面的有用性。