Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland; Division of Cardiology, University Hospital Basel, Basel, Switzerland.
Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
Transl Res. 2014 Apr;163(4):307-20. doi: 10.1016/j.trsl.2013.12.005. Epub 2013 Dec 11.
Recent insights into myocardial biology uncovered a hereto unknown regenerative capacity of the adult heart. The discovery of dividing cardiomyocytes and the identification and characterization of cardiac stem and progenitor cells with myogenic and angiogenic potential have generated new hopes that cardiac regeneration and repair might become a therapeutic option. During the past decade, multiple candidate cells have been proposed for cardiac regeneration, and their mechanisms of action in the myocardium have been explored. Initial clinical trials have focused on the use of bone marrow-derived cells to promote myocardial regeneration in ischemic heart disease and have yielded very mixed results, with no clear signs of clinically meaningful functional improvement. Although the efficiency of bona fide cardiomyocyte generation is generally low, stem cells delivered into the myocardium act mainly via paracrine mechanisms. More recent studies taking advantage of cardiac committed cells (eg, resident cardiac progenitor cells or primed cardiogenic mesenchymal stem cells) showed promising results in first clinical pilot trials. Also, transplantation of cardiomyogenic cells generated by induced pluripotent stem cells and genetic reprogramming of dividing nonmyocytes into cardiomyocytes may constitute attractive new regenerative approaches in cardiovascular medicine in the future. We discuss advantages and limitations of specific cell types proposed for cell-based therapy in cardiology and give an overview of the first clinical trials using this novel therapeutic approach in patients with cardiovascular disease.
近年来，人们对心肌生物学的深入了解揭示了成年心脏迄今未知的再生能力。发现有分裂的心肌细胞，以及具有成肌和成血管潜能的心脏干细胞和祖细胞的鉴定和特征描述，为心脏再生和修复可能成为一种治疗选择带来了新的希望。在过去的十年中，已经提出了多种候选细胞用于心脏再生，并且已经探索了它们在心肌中的作用机制。最初的临床试验集中在利用骨髓来源的细胞来促进缺血性心脏病中的心肌再生，并且得到了非常混杂的结果，没有明显的迹象表明具有临床意义的功能改善。尽管真正的心肌细胞生成效率通常较低，但注入心肌的干细胞主要通过旁分泌机制起作用。最近的一些研究利用心脏定向细胞（例如，驻留的心脏祖细胞或预先诱导的成心肌间充质干细胞），在首次临床试点试验中显示出有希望的结果。此外，利用诱导多能干细胞生成的心肌细胞和成肌细胞以及将分裂的非肌细胞遗传重编程为心肌细胞的方法，可能在未来构成心血管医学中吸引人的新再生方法。我们讨论了拟用于心脏病学细胞治疗的特定细胞类型的优点和局限性，并概述了在心血管疾病患者中使用这种新治疗方法的首次临床试验。
