Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart.

Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart.
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DOI:
10.1002/emmm.201201737
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发表时间:
2013-02
影响因子:
11.1
通讯作者:
Marban, Eduardo
Marban, Eduardo
中科院分区:
医学1区
文献类型:
--
作者:
Malliaras, Konstantinos;Zhang, Yiqiang;Seinfeld, Jeffrey;Galang, Giselle;Tseliou, Eleni;Cheng, Ke;Sun, Baiming;Aminzadeh, Mohammad;Marban, Eduardo

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心肌梗死患者的心肌细胞(CDCs)可以再生梗死心肌。然而,新形成的心肌细胞是来源于成体心肌细胞的增殖还是来源于内源性干细胞的分化仍不清楚。使用遗传命运映射标记常驻肌细胞结合长期BrdU脉冲,我们研究了出生后的正常,梗死和细胞治疗的成年哺乳动物心脏心肌发生的起源。在正常小鼠心脏中,心肌细胞更新主要通过驻留心肌细胞的增殖发生,增殖率为1.3-4%/年。MI后,新的心肌细胞从祖细胞以及预先存在的心肌细胞中产生。CDC的移植上调宿主心肌细胞周期和内源性祖细胞的募集,同时增强心脏功能并增加存活心肌。观察到的现象不能用心肌细胞多倍化、双/多核化、细胞融合或DNA修复来解释。因此,CDCs通过差异上调内源性细胞增殖的两种机制诱导心肌再生。
Cardiosphere-derived cells (CDCs) have been shown to regenerate infarcted myocardium in patients after myocardial infarction (MI). However, whether the cells of the newly formed myocardium originate from the proliferation of adult cardiomyocytes or from the differentiation of endogenous stem cells remains unknown. Using genetic fate mapping to mark resident myocytes in combination with long-term BrdU pulsing, we investigated the origins of postnatal cardiomyogenesis in the normal, infarcted and cell-treated adult mammalian heart. In the normal mouse heart, cardiomyocyte turnover occurs predominantly through proliferation of resident cardiomyocytes at a rate of ∼1.3–4%/year. After MI, new cardiomyocytes arise from both progenitors as well as pre-existing cardiomyocytes. Transplantation of CDCs upregulates host cardiomyocyte cycling and recruitment of endogenous progenitors, while boosting heart function and increasing viable myocardium. The observed phenomena cannot be explained by cardiomyocyte polyploidization, bi/multinucleation, cell fusion or DNA repair. Thus, CDCs induce myocardial regeneration by differentially upregulating two mechanisms of endogenous cell proliferation.
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