Bryant Donald Marion, O'Meara Caitlin Claire, Ho Nhi Ngoc, Gannon Joseph, Cai Lei, Lee Richard Theodore
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, The Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02139, USA.
J Mol Cell Cardiol. 2015 Feb;79:315-8. doi: 10.1016/j.yjmcc.2014.12.011. Epub 2014 Dec 19.
The finding that neonatal mice are able to regenerate myocardium after apical resection has recently been questioned. We determined if heart regeneration is influenced by the size of cardiac resection and whether surgical retraction of the ventricular apex results in an increase in cardiomyocyte cell cycle activity. We performed moderate or large apical ventricular resections on neonatal mice and quantified scar infiltration into the left ventricular wall at 21 days post-surgery. Moderately resected hearts had 15±2% of the wall infiltrated by a collagen scar; significantly greater scar infiltration (23±4%) was observed in hearts with large resections. Resected hearts had higher levels of cardiomyocyte cell cycle activity relative to sham hearts. Surgically retracting the ventricle often resulted in fibrosis and induced cardiomyocyte cell cycle activity that were comparable to that of resected hearts. We conclude that apical resection in neonatal mice induces cardiomyocyte cell cycle activity and neomyogenesis, although scarring can occur. Surgical technique and definition of approach to assessing the extent of regeneration are both critical when using the neonatal mouse apical resection model.
新生儿小鼠在心尖切除术后能够再生心肌这一发现最近受到了质疑。我们确定了心脏再生是否受心脏切除大小的影响,以及心室尖的手术牵拉是否会导致心肌细胞细胞周期活性增加。我们对新生小鼠进行了中度或大型心尖心室切除术,并在术后21天对左心室壁的瘢痕浸润进行了量化。中度切除的心脏有15±2%的壁被胶原瘢痕浸润;在大型切除的心脏中观察到明显更大的瘢痕浸润(23±4%)。与假手术心脏相比,切除的心脏具有更高水平的心肌细胞细胞周期活性。手术牵拉心室常导致纤维化并诱导心肌细胞细胞周期活性,这与切除的心脏相当。我们得出结论,新生小鼠的心尖切除诱导心肌细胞细胞周期活性和新肌生成,尽管会发生瘢痕形成。当使用新生小鼠心尖切除模型时,手术技术和评估再生程度的方法定义都至关重要。