Sami Nabeel, Parikh Manish A, Frishman William H, Peterson Stephen J
From the Department of Medicine, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY.
Weill Department of Medicine, Weill Cornell Medicine, New York, NY.
Cardiol Rev. 2025 Jun 18. doi: 10.1097/CRD.0000000000000972.
Myocardial infarction and heart failure remain among the leading global causes of morbidity and mortality, mainly due to the irreversible loss of cardiomyocytes and the human heart's inherently limited regenerative capacity. Cardiac regeneration has emerged as a transformative frontier in cardiovascular medicine in response to this clinical and biological impasse. This review examines current approaches to rebuilding damaged heart tissue and improving cardiac function. Early investigations into cell-based therapies, particularly mesenchymal stem cells, and bone marrow-derived mononuclear cells, showed modest improvements in heart function. These benefits appeared to arise primarily through paracrine signaling, rather than direct tissue regeneration. More recently, researchers have focused on extracellular vesicles and exosomes, acellular messengers that deliver molecular signals to encourage new blood vessel growth, reduce inflammation, and promote cell survival. Breakthroughs in direct cardiac reprogramming now make it possible to convert fibroblasts into cardiomyocyte-like cells, while induced pluripotent stem cell-derived cardiomyocytes open new doors for personalized disease modeling and potential myocardial reconstruction. Advances in gene editing, most notably clustered regularly interspaced short palindromic repeats/Cas9, are elevating the precision and efficiency of regenerative interventions. Finally, synthetic biology and tissue engineering innovations are accelerating the development of physiological cardiac tissue patches and driving the aspiration of a fully implantable bioartificial heart. These multidisciplinary innovations are redefining the boundaries of cardiac care and bringing the prospect of myocardial regeneration increasingly within reach.
心肌梗死和心力衰竭仍然是全球发病和死亡的主要原因，主要是由于心肌细胞的不可逆损失以及人类心脏固有的有限再生能力。作为对这一临床和生物学困境的回应，心脏再生已成为心血管医学中一个变革性的前沿领域。本综述探讨了目前重建受损心脏组织和改善心脏功能的方法。早期对基于细胞的疗法，特别是间充质干细胞和骨髓来源的单核细胞的研究表明，心脏功能有适度改善。这些益处似乎主要通过旁分泌信号产生，而非直接的组织再生。最近，研究人员将重点放在了细胞外囊泡和外泌体上，这些无细胞信使传递分子信号以促进新血管生长、减轻炎症并促进细胞存活。直接心脏重编程的突破现在使得将成纤维细胞转化为心肌样细胞成为可能，而诱导多能干细胞衍生的心肌细胞为个性化疾病建模和潜在的心肌重建打开了新的大门。基因编辑的进展，最显著的是成簇规律间隔短回文重复序列/Cas9，正在提高再生干预的精度和效率。最后，合成生物学和组织工程创新正在加速生理性心脏组织贴片的开发，并推动人们对完全可植入生物人工心脏的憧憬。这些多学科创新正在重新定义心脏护理的边界，并使心肌再生的前景越来越触手可及。
