Psaltis Peter J, Schwarz Nisha, Toledo-Flores Deborah, Nicholls Stephen J
Co-Director of Vascular Research Centre, Heart Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, Australia 5000.
Curr Cardiol Rev. 2016;12(3):195-215. doi: 10.2174/1573403x12666160606121858.
The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management.
心肌病和心力衰竭（HF）的发病机制是由心室心肌在亚细胞、细胞和细胞外水平的复杂变化所支撑的。尽管传统的HF治疗在降低死亡率和发病率方面取得了诸多成效，但它们并不能充分解决重构心室中心肌细胞数量的减少问题。最初为解决这一问题而设想的HF细胞移植，在过去二十年中已经经历了几个发展阶段。在缺血性和非缺血性心肌病的临床前模型中，已经采用了各种细胞类型和递送途径，并取得了积极效果，在心肌重构、收缩和舒张功能、灌注、纤维化、炎症、代谢和电生理方面都观察到了多效性益处。在很大程度上，这些有益作用现在归因于移植干细胞促进内源性心脏修复过程的间接旁分泌能力。早期人体研究也取得了有希望的结果，尽管这些结果相对有限且有些不一致。本综述详细介绍了目前关于使用多能干细胞和成年来源祖细胞治疗心肌病和HF的临床前和临床证据。它概述了到目前为止所学到的重要经验教训，并在这个令人兴奋的领域的前景与仍需在各级研究中解决的关键挑战和问题之间取得平衡，以确保细胞治疗通过增加HF管理手段来充分发挥其潜力。
