Apolínová Kateřina, Pérez Ferran Arqué, Dyballa Sylvia, Coppe Benedetta, Mercader Huber Nadia, Terriente Javier, Di Donato Vincenzo
ZeClinics SL, Barcelona, Spain.
Biomedicine, Department of Medicine and Life Sciences, Faculty of Health and Life Sciences, Pompeu Fabra University, Barcelona, Spain.
Front Cell Dev Biol. 2024 May 10;12:1384423. doi: 10.3389/fcell.2024.1384423. eCollection 2024.
Cardiovascular disease is the leading cause of death worldwide with myocardial infarction being the most prevalent. Currently, no cure is available to either prevent or revert the massive death of cardiomyocytes that occurs after a myocardial infarction. Adult mammalian hearts display a limited regeneration capacity, but it is insufficient to allow complete myocardial recovery. In contrast, the injured zebrafish heart muscle regenerates efficiently through robust proliferation of pre-existing myocardial cells. Thus, zebrafish allows its exploitation for studying the genetic programs behind cardiac regeneration, which may be present, albeit dormant, in the adult human heart. To this end, we have established ZebraReg, a novel and versatile automated platform for studying heart regeneration kinetics after the specific ablation of cardiomyocytes in zebrafish larvae. In combination with automated heart imaging, the platform can be integrated with genetic or pharmacological approaches and used for medium-throughput screening of presumed modulators of heart regeneration. We demonstrate the versatility of the platform by identifying both anti- and pro-regenerative effects of genes and drugs. In conclusion, we present a tool which may be utilised to streamline the process of target validation of novel gene regulators of regeneration, and the discovery of new drug therapies to regenerate the heart after myocardial infarction.
心血管疾病是全球主要的死亡原因，其中心肌梗死最为常见。目前，尚无治愈方法可预防或逆转心肌梗死后发生的心肌细胞大量死亡。成年哺乳动物心脏的再生能力有限，不足以实现心肌的完全恢复。相比之下，受伤的斑马鱼心肌可通过已有心肌细胞的强劲增殖而有效再生。因此，斑马鱼可用于研究心脏再生背后的遗传程序，这些程序可能存在于成年人类心脏中，尽管处于休眠状态。为此，我们建立了ZebraReg，这是一个新颖且通用的自动化平台，用于研究斑马鱼幼体心肌细胞特异性消融后的心脏再生动力学。结合自动心脏成像，该平台可与遗传或药理学方法相结合，用于对假定的心脏再生调节剂进行中通量筛选。我们通过鉴定基因和药物的抗再生和促再生作用，证明了该平台的多功能性。总之，我们提供了一种工具，可用于简化新型再生基因调节剂的靶点验证过程，以及发现心肌梗死后促进心脏再生的新药物疗法。
