Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration.
Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration.
复制标题
脱细胞斑马鱼心脏外基质会诱导哺乳动物心脏再生。
DOI：
10.1126/sciadv.1600844
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发表时间：
2016-11
期刊：
影响因子：
13.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Chen WC;Wang Z;Missinato MA;Park DW;Long DW;Liu HJ;Zeng X;Yates NA;Kim K;Wang Y
去细胞斑马鱼心肌细胞外基质可诱导哺乳动物急性心肌梗死后心脏再生。心脏病发作是一个全球性的健康问题，导致显著的发病率、死亡率和医疗保健负担。成年人的心脏在受伤后再生能力非常有限。然而，进化上原始的物种通常比哺乳动物具有更高的再生能力。细胞外基质（ECM）可能有助于这种差异。哺乳动物心脏ECM可能不是心脏再生的最佳诱导，因为在受伤的成年哺乳动物心脏中纤维化而不是再生反应。鉴于成年斑马鱼心脏的高再生能力，我们假设由正常或愈合心脏制成的脱细胞斑马鱼心脏ECM（zECM）可以诱导哺乳动物心脏再生。使用斑马鱼和小鼠作为低等脊椎动物和哺乳动物的代表性物种，我们表明，zECM，特别是愈合品种的单次给药，使心脏功能恢复和再生的成年小鼠心脏组织急性心肌梗死后。zECM处理组表现出剩余心肌细胞和多个心脏前体细胞群的增殖以及心肌细胞中ErbB2表达的再激活。此外，zECM在体外对人心脏前体细胞群体表现出促增殖和趋化作用。这些有助于结构保存，并与zECM处理的心脏中显著更高的心脏收缩功能，特别是更少的左心室扩张，以及比用盐水或脱细胞的成年小鼠心脏ECM处理的对照动物实质上更有弹性的心肌相关。ErbB2活性的抑制消除了zECM施用的有益作用，表明ErbB2信号传导可能参与zECM介导的再生。本研究从传统的重点出发，对哺乳动物细胞外基质，并介绍了一种新的方法，心脏组织再生。
Mammalian heart regeneration after acute heart attacks can be induced by decellularized zebrafish cardiac extracellular matrix. Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts. Given the high regenerative capacity of adult zebrafish hearts, we hypothesize that decellularized zebrafish cardiac ECM (zECM) made from normal or healing hearts can induce mammalian heart regeneration. Using zebrafish and mice as representative species of lower vertebrates and mammals, we show that a single administration of zECM, particularly the healing variety, enables cardiac functional recovery and regeneration of adult mouse heart tissues after acute myocardial infarction. zECM-treated groups exhibit proliferation of the remaining cardiomyocytes and multiple cardiac precursor cell populations and reactivation of ErbB2 expression in cardiomyocytes. Furthermore, zECM exhibits pro-proliferative and chemotactic effects on human cardiac precursor cell populations in vitro. These contribute to the structural preservation and correlate with significantly higher cardiac contractile function, notably less left ventricular dilatation, and substantially more elastic myocardium in zECM-treated hearts than control animals treated with saline or decellularized adult mouse cardiac ECM. Inhibition of ErbB2 activity abrogates beneficial effects of zECM administration, indicating the possible involvement of ErbB2 signaling in zECM-mediated regeneration. This study departs from conventional focuses on mammalian ECM and introduces a new approach for cardiac tissue regeneration.