Yang Jianchang
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Cells. 2024 Dec 4;13(23):2002. doi: 10.3390/cells13232002.
Heart disease, including myocardial infarction (MI), remains a leading cause of morbidity and mortality worldwide, necessitating the development of more effective regenerative therapies. Direct reprogramming of cardiomyocyte-like cells from resident fibroblasts offers a promising avenue for myocardial regeneration, but its efficiency and consistency in generating functional cardiomyocytes remain limited. Alternatively, reprogramming induced cardiac progenitor cells (iCPCs) could generate essential cardiac lineages, but existing methods often involve complex procedures. These limitations underscore the need for advanced mechanistic insights and refined reprogramming strategies to improve reparative outcomes in the heart. Partial cellular fate transitions, while still a relatively less well-defined area and primarily explored in longevity and neurobiology, hold remarkable promise for cardiac repair. It enables the reprogramming or rejuvenation of resident cardiac cells into a stem or progenitor-like state with enhanced cardiogenic potential, generating the reparative lineages necessary for comprehensive myocardial recovery while reducing safety risks. As an emerging strategy, partial cellular fate transitions play a pivotal role in reversing myocardial infarction damage and offer substantial potential for therapeutic innovation. This review will summarize current advances in these areas, including recent findings involving two transcription factors that critically regulate stemness and cardiogenesis. It will also explore considerations for further refining these approaches to enhance their therapeutic potential and safety.
心脏病，包括心肌梗死（MI），仍然是全球发病和死亡的主要原因，因此需要开发更有效的再生疗法。将驻留成纤维细胞直接重编程为心肌样细胞为心肌再生提供了一条有前景的途径，但其在产生功能性心肌细胞方面的效率和一致性仍然有限。或者，重编程诱导的心脏祖细胞（iCPCs）可以产生重要的心脏谱系，但现有方法通常涉及复杂的程序。这些局限性凸显了需要深入的机制见解和优化的重编程策略，以改善心脏的修复效果。部分细胞命运转变，虽然仍是一个相对定义不明确的领域，主要在长寿和神经生物学中进行探索，但对心脏修复具有显著的前景。它能够将驻留心脏细胞重编程或恢复活力至干细胞或祖细胞样状态，增强其心脏发生潜力，产生全面心肌恢复所需的修复谱系，同时降低安全风险。作为一种新兴策略，部分细胞命运转变在逆转心肌梗死损伤中起关键作用，并为治疗创新提供了巨大潜力。本综述将总结这些领域的当前进展，包括涉及两个关键调节干性和心脏发生的转录因子的最新发现。它还将探讨进一步优化这些方法以增强其治疗潜力和安全性的考虑因素。
