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首页> 外文期刊>Acta biomaterialia >Decellularized neonatal cardiac extracellular matrix prevents widespread ventricular remodeling in adult mammals after myocardial infarction
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Decellularized neonatal cardiac extracellular matrix prevents widespread ventricular remodeling in adult mammals after myocardial infarction

机译：脱细胞的新生儿心肌细胞外基质可防止心肌梗死后成年哺乳动物的广泛心室重塑

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摘要

Heart disease remains a leading killer in western society and irreversibly impacts the lives of millions of patients annually. While adult mammals do not possess the ability to regenerate functional cardiac tissue, neonatal mammals are capable of robust cardiomyocyte proliferation and regeneration within a week of birth. Given this change in regenerative function through development, the extracellular matrix (ECM) from adult tissues may not be conducive to promoting cardiac regeneration, although conventional ECM therapies rely exclusively on adult-derived tissues. Therefore the potential of ECM derived from neonatal mouse hearts (nmECM) to prevent adverse ventricular remodeling in adults was investigated using an in vivo model of acute myocardial infarction (MI). Following a single administration of nmECM, we observed a significant improvement in heart function while adult heart-derived ECM (amECM) did not improve these parameters. Treatment with nmECM limits scar expansion in the left ventricle and promotes revascularization of the injured region. Furthermore, nmECM induced expression of the ErbB2 receptor, simulating a neonatal-like environment and promoting neuregulin-1 associated cardiac function. Inhibition of the ErbB2 receptor effectively prevents these actions, suggesting its role in the context of nmECM as a therapy. This study shows the potential of a neonatal-derived biological material in vivo, diverting from the conventional use of adult-derived ECM therapies in research and the clinic.
机译：心脏疾病仍然是西方社会的一个主要杀手和不可逆的影响每年数以百万计患者的生命。虽然成年哺乳动物不具备再生功能的心脏组织的能力，新生哺乳动物能够在出生一周内稳健的心肌细胞增殖和再生。鉴于这种变化在通过发展再生功能，从成年组织中的细胞外基质（ECM）可能不利于促进心脏再生，虽然常规ECM疗法完全依赖于成人来源的组织。因此ECM的电位从新生小鼠心脏（nmECM）衍生的，以防止使用急性心肌梗死（MI）的体内模型不良心室成人重塑进行了研究。继nmECM的单一管理，我们在心脏功能观察到显著的改善，而成人心脏来源的ECM（amECM）并不能改善这些参数。治疗nmECM限制了左心室疤痕扩张和促进损伤部位的血运重建。此外，nmECM诱导ErbB2受体的表达，模拟新生儿状环境，促进神经调节蛋白-1相关的心脏功能。 ErbB2受体的抑制有效地防止这些行为，这表明其在作为治疗nmECM的上下文中的作用。这项研究表明体内新生儿衍生的生物材料，与传统使用的研究和临床成人来源的ECM治疗转移的潜力。

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