Ischemic tolerance and cardiac repair in the African spiny mouse

Ischemic heart disease and by extension myocardial infarction is the primary cause of death worldwide, necessitating regenerative therapies to restore heart function. Current models of heart regeneration are restricted in that they are not of adult mammalian origin, precluding the study of class-specific traits that have emerged throughout evolution, and reducing translatability of research findings to humans. Here, we overcome those restrictions by introducing the African spiny mouse (Acomys spp.), a murid rodent that has recently been found to exhibit bona fide regeneration of the back skin and ear pinna. We show that spiny mice exhibit tolerance to myocardial infarction through superior survivability, improved ventricular conduction, smaller scar size, and near-absence of cardiac remodeling. Critically, spiny mice display increased vascularization and cardiomyocyte expansion, with an associated improvement in heart function. These findings present new avenues for mammalian heart research by leveraging unique tissue properties of the spiny mouse.

缺血性心脏病及其继发的心肌梗死是全球首要致死病因，亟需开发再生疗法以恢复心脏功能。现有心脏再生模型存在显著局限：其样本均非源自成年哺乳动物，既无法研究进化过程中形成的类群特异性特征，也降低了研究结果向人类临床转化的可行性。为此，我们引入非洲刺毛鼠（African spiny mouse, Acomys spp.）——一种新近被证实可实现背部皮肤与耳郭真正再生的鼠科啮齿动物——以突破上述研究瓶颈。研究表明，刺毛鼠对心肌梗死具有良好耐受性，具体表现为存活率更高、心室传导功能改善、瘢痕面积更小，且几乎不发生心脏重构。尤为关键的是，刺毛鼠可增强血管生成与心肌细胞增殖，并伴随心脏功能的显著改善。本研究通过利用刺毛鼠独特的组织特性，为哺乳动物心脏研究开辟了全新方向。