心肌细胞能否自己复原？科学家们是否能够帮助它们做到？发表在《自然》（Nature）杂志上的两篇论文表明心肌细胞可以以非常低的速率自我更新，但一种遗传学技术可以促使它们做得更好。这些结果给人们带来了希望，或许能够诱导心血管疾病损伤的心脏自我再生。
高倍显微镜下的心肌细胞，其细胞横纹不似骨骼肌般明显，细胞成分叉状，细胞核为圆形位于细胞中央，心肌细胞间以肌间盘相互连接。
心肌无法很好的自我更新。研究人员希望通过寻找心脏中具有这一功能的细胞群来帮助到这一过程，并提高这种能力。然而找到这些再生细胞的证据，或是评估它们的能力，一直以来并非是一件易事。
两篇Nature文章旨在触及问题的核心。在第一篇论文中，由布莱根妇女医院（Brigham and Women’s Hospital）和哈佛大学医学院Richard Lee领导的一个研究小组，在小鼠中追踪了心肌细胞的起源和命运。Lee和同事们发现只有小部分的心脏细胞（不到1%）通常能够自我更新。在心脏病发作后，这一比例上升，但也只有3%。
华盛顿大学从事心脏再生研究的Charles (Chuck) Murry说：“这些研究打破了心脏具有强大再生能力的概念。”
心脏的希望
Lee实验室成员、论文的共同作者Matthew Steinhauser说：“发现有这些细胞存在是鼓舞人心的，如果心脏存在一些生成新心肌细胞的能力，我们可以此为支点开展工作。”
在第二篇论文中，另一个研究小组就如何提高心肌细胞再生能力展开了研究。意大利国际遗传工程和生物技术中心的Mauro Giacca和同事们采用microRNAs刺激了心肌细胞开始再生。
研究人员对数百个microRNAs进行了筛查，检测了它们促进小鼠和大鼠心肌细胞增殖的能力。研究小组随后在活体小鼠中诱导了心脏病发作，证实两种特殊的microRNAs可以帮助重新修复受损的心脏，以致心脏能够几乎正常地运作。在两个月后，心脏病发作破坏的组织减少了一半面积，心脏泵血能力得到显著改善。
Giacca表示还需要在更大的、具有更似人类心脏的动物模型中进一步检测这些microRNAs。其他的科学家们也希望看到这些结果得到证实。
Murry 说：“了解这一领域的人看到过许多心肌再生的策略并没有经受住时间的考验。如果这一研究可以再现，这将是一个重大的突破。”
Mammalian heart renewal by pre-existing cardiomyocytes
Samuel E. Senyo, Matthew L. Steinhauser, Christie L. Pizzimenti, Vicky K. Yang, Lei Cai, Mei Wang, Ting-Di Wu, Jean-Luc Guerquin-Kern, Claude P. Lechene & Richard T. Lee
Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes1. Other studies suggest that new cardiomyocytes are born at a very low rate2, 3, 4, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse–chase approaches—genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry—that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
文献链接：Mammalian heart renewal by pre-existing cardiomyocytes
Functional screening identifies miRNAs inducing cardiac regeneration
Ana Eulalio, Miguel Mano, Matteo Dal Ferro, Lorena Zentilin, Gianfranco Sinagra, Serena Zacchigna & Mauro Giacca
In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.
文献链接：Functional screening identifies miRNAs inducing cardiac regeneration
