van der Pol Atze, Bouten Carlijn V C
Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, Netherlands.
Front Cardiovasc Med. 2021 May 20;8:682342. doi: 10.3389/fcvm.2021.682342. eCollection 2021.
Tissue homeostasis is perturbed by stressful events, which can lead to organ dysfunction and failure. This is particularly true for the heart, where injury resulting from myocardial infarction or ischemic heart disease can result in a cascading event ultimately ending with the loss of functional myocardial tissue and heart failure. To help reverse this loss of healthy contractile tissue, researchers have spent decades in the hopes of characterizing a cell source capable of regenerating the injured heart. Unfortunately, these strategies have proven to be ineffective. With the goal of truly understanding cardiac regeneration, researchers have focused on the innate regenerative abilities of zebrafish and neonatal mammals. This has led to the realization that although cells play an important role in the repair of the diseased myocardium, inducing cardiac regeneration may instead lie in the composition of the extra cellular milieu, specifically the extra cellular matrix. In this review we will briefly summarize the current knowledge regarding cell sources used for cardiac regenerative approaches, since these have been extensively reviewed elsewhere. More importantly, by revisiting innate cardiac regeneration observed in zebrafish and neonatal mammals, we will stress the importance the extra cellular matrix has on reactivating this potential in the adult myocardium. Finally, we will address how we can harness the ability of the extra cellular matrix to guide cardiac repair thereby setting the stage of next generation regenerative strategies.
应激事件会扰乱组织内稳态，进而可能导致器官功能障碍和衰竭。心脏尤其如此，心肌梗死或缺血性心脏病所导致的损伤可能引发一系列级联反应，最终以功能性心肌组织丧失和心力衰竭告终。为了帮助逆转健康收缩性组织的这种损失，研究人员花费了数十年时间，希望找到一种能够使受损心脏再生的细胞来源。不幸的是，这些策略已被证明是无效的。为了真正理解心脏再生，研究人员将重点放在了斑马鱼和新生哺乳动物的先天再生能力上。这使人们认识到，尽管细胞在患病心肌的修复中起着重要作用，但诱导心脏再生可能反而取决于细胞外环境的组成，特别是细胞外基质。在本综述中，我们将简要总结目前关于用于心脏再生方法的细胞来源的知识，因为这些内容在其他地方已有广泛综述。更重要的是，通过回顾在斑马鱼和新生哺乳动物中观察到的先天心脏再生，我们将强调细胞外基质在激活成年心肌这种潜能方面的重要性。最后，我们将探讨如何利用细胞外基质引导心脏修复的能力，从而为下一代再生策略奠定基础。
