2012年12月5日讯 /生物谷BIOON/ --尽管近期的研究表明,在成年哺乳动物心脏中有新的心肌细胞产生,但这些新的心肌细胞的更新周期、来源仍然未知。来自布里格姆妇女医院(BWH)的研究人员,利用了一种新方法来鉴别这些新的心肌细胞,并描述了它们的起源。该项研究的结果已发表于本期Nature。
一种复杂的成像系统(MIMS)演示了成年哺乳动物心脏中的细胞分裂。
“心肌细胞多久更新,这一问题极难回答,因为需要一种新的技术来帮助了解这个过程。我们的研究结果令人兴奋,因为利用这种新方法,我们能够展示新的心肌细胞。多重同位素成像质谱(Multi-isotope Imaging Mass Spectrometry,MIMS)技术由合作者Claude Lechene博士开发,我们利用该技术解决了心肌细胞再生的问题。”研究人员Richard T.Lee说道。“这些数据解决了围绕新的心肌细胞生成的谜团。”
在小鼠模型中,研究人员通过基因技术使现有的心肌细胞表达一种绿色荧光蛋白。并在接下来的数个月里,利用多同位素成像质谱(MIMS)来检查新的心肌细胞的生成。
研究人员惊奇地发现,新的心肌细胞主要源自现有的心肌细胞,而不是干细胞。即使在心脏病发作(heart attack)情况下,大部分新的心肌细胞仍来源于现有细胞。而此前认为,心脏病发作时,心脏内的干细胞被激活。
这些数据表明,现有的心肌细胞,是正常成年哺乳动物心肌细胞更新(cardiomyocyte replacement)及心肌损伤后心肌稳态(myocardial homeostasis)的最主要来源。
我们的数据显示,新的心肌细胞生成主要有成年心肌细胞负责。随着慢慢变老,我们失去了某种能力,来生成新的心肌细胞。这意味着,在下半辈子的生活中,我们将失去重建心脏的能力,而这时候大多数心脏疾病正向我们袭来。如果我们能揭示,为什么这种情况会发生,我们可能能够释放一些心脏再生的潜能。(生物谷bioon.com)
编译自:The Birth of New Cardiac Cells: Where New Heart Cells Come from
doi:10.1038/nature11682
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Mammalian heart renewal by pre-existing cardiomyocytes
Samuel E. Senyo, Matthew L. Steinhauser, Christie L. Pizzimenti, et al
Abstract: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.