De novo cardiomyocytes from within the activated adult heart after injury.
De novo cardiomyocytes from within the activated adult heart after injury.
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DOI：
10.1038/nature10188
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发表时间：
2011-06-08
期刊：
影响因子：
64.8
通讯作者：
Riley, Paul R.
中科院分区：
文献类型：
--
作者：
Smart, Nicola;Bollini, Sveva;Dube, Karina N.;Vieira, Joaquim M.;Zhou, Bin;Davidson, Sean;Yellon, Derek;Riegler, Johannes;Price, Anthony N.;Lythgoe, Mark F.;Pu, William T.;Riley, Paul R.
心血管再生医学的一个重要瓶颈是在缺血性心脏病和急性心肌梗死后，干细胞/祖细胞的可行来源的鉴定。相对于细胞移植而言，一种理想的治疗方法是刺激常驻源，从而避免移植物存活受限、损伤部位归巢受限和宿主免疫排斥等问题。在这里，我们在小鼠身上证明，成年心脏包含一个驻留的干细胞或祖细胞群，它们有可能在心肌梗死后贡献真正的终分化心肌细胞。我们通过胸腺酶β4（一种先前被证明可以恢复损伤的成体心外膜源性祖细胞血管潜能的肽）引发的关键胚胎心外膜基因Wilm 's tumor 1 （Wt1）的重新表达，揭示了激活的成体祖细胞的一个新的遗传标签。越来越多的证据表明，心肌细胞起源于心外膜，胚胎重编程导致心肌细胞群的动员，并伴随分化产生新生心肌细胞。细胞移植证实了祖细胞的来源，标记供体细胞的染色体描绘显示在没有细胞融合的情况下转分化为肌细胞命运。图中显示，衍生心肌细胞在结构和功能上与常驻肌相结合；因此，刺激这个成人祖细胞库代表了人类缺血性心脏病驻留细胞治疗的重要一步。
A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction. A therapeutic ideal—relative to cell transplantation—would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm’s tumour 1 (Wt1), through priming by thymosin β4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards residentcell-based therapy in human ischaemic heart disease.
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影响因子：
64.8
作者：
Laugwitz, KL;Moretti, A;Chien, KR
通讯作者：
Chien, KR
影响因子：
5
作者：
Limana, Federica;Bertolami, Chiara;Capogrossi, Maurizio C.
通讯作者：
Capogrossi, Maurizio C.
影响因子：
3.2
作者：
Moorman, AFM;Houweling, AC;Christoffels, VM
通讯作者：
Christoffels, VM
影响因子：
64.8
作者：
Zhou, Bin;Ma, Qing;Pu, William T.
通讯作者：
Pu, William T.
胸腺素 beta4 介导的 PKC 激活对于成年小鼠体内启动胚胎冠状动脉发育程序和心外膜祖细胞激活至关重要。
影响因子：
5
作者：
Bock-Marquette, Ildiko;Shrivastava, Santwana;Pipes, G. C. Teg;Thatcher, Jeffrey E.;Blystone, Allissa;Shelton, John M.;Galindo, Cristi L.;Melegh, Bela;Srivastava, Deepak;Olson, Eric N.;DiMaio, J. Michael
通讯作者：
DiMaio, J. Michael