Centola Marco, Schuleri Karl H, Lardo Albert C, Hare Joshua M
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
G Ital Cardiol (Rome). 2008 Apr;9(4):234-50.
Ischemic heart disease is a major public health problem in the industrialized and developing world. Despite advances in myocardial reperfusion strategies and novel pharmacological approaches, ther apies directed towards the deleterious consequences of acute and chronic myocardial ischemic damage remain limited. In recent years the biological dogma of the heart as a "postmitotic organ" has been challenged. Myocyte replication and myocardial regeneration have been documented in the human heart after myocardial infarction and in chronic ischemic heart failure. In addition, experimental animal studies and clinical trials suggest that the transfer of stem and progenitor cells into the myocardium has a favorable impact on tissue perfusion and contractile performance. Neovascularization and myocyte formation have been described. Differentiation of administered stem cells, cell fusion and release of paracrine signals by injected stem cells are currently discussed as underlying mechanisms. Recently, the mobilization of endogenous cardiac stem cells is debated as a potential target of cardiac repair. This intriguing new knowledge generated by basic and clinical scientists will lay the foundation for novel therapeutic strategies in the near future and change clinical practice in cardiology. In this commentary, we briefly review the characterization of the variety of stem cell populations used for cardiac repair, discuss the potential mechanisms of cardiac regenerative therapy, and evaluate the current clinical applications of this innovative approach to treat ischemic heart disease.
缺血性心脏病是工业化国家和发展中国家的一个主要公共卫生问题。尽管在心肌再灌注策略和新型药理学方法方面取得了进展,但针对急性和慢性心肌缺血损伤有害后果的治疗方法仍然有限。近年来,心脏作为“终末有丝分裂器官”的生物学教条受到了挑战。在心肌梗死后的人类心脏以及慢性缺血性心力衰竭中,已记录到心肌细胞复制和心肌再生。此外,实验动物研究和临床试验表明,将干细胞和祖细胞移植到心肌中对组织灌注和收缩功能有有利影响。已描述了新生血管形成和心肌细胞形成。目前正在讨论所注入干细胞的分化、细胞融合以及旁分泌信号的释放作为潜在机制。最近,内源性心脏干细胞的动员作为心脏修复的潜在靶点受到了争论。基础科学家和临床科学家所产生的这一引人入胜的新知识将在不久的将来为新型治疗策略奠定基础,并改变心脏病学的临床实践。在这篇评论中,我们简要回顾用于心脏修复的各种干细胞群体的特征,讨论心脏再生治疗的潜在机制,并评估这种创新方法治疗缺血性心脏病的当前临床应用。