Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the post-ischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit and strategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel "pharmaco-optimizer" as well as genetic modifications.

中文翻译：

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优化干细胞进行心脏修复：再生心脏病学的现状和新领域。

细胞疗法具有改善缺血性心脏的愈合，重新填充受伤的心肌并恢复心脏功能的潜力。干细胞疗法的巨大希望和潜力已广为人知，但有关心血管疾病的细胞疗法的最新试验结果却不一致，数据不一致，从而重新解决了关于干细胞治疗缺血性心脏病的功效的争议和悬而未决的问题。这些争议被认为是由于临床试验方法的缺乏统一性，干细胞的基本修复机制的不确定性，有关最适合使用的细胞群的问题，正确的递送方法以及与梗塞时间有关的时机而引起的。 ，以及干细胞存活率和移植性差，特别是在患病的微环境中，这被普遍认为是任何形式的细胞治疗的主要障碍。实际上，心脏衰竭的微环境表现出病理性的缺氧，氧化和炎性应激源，损害了移植细胞的存活。因此，为了观察到任何显着的治疗益处，需要在保留或更好地改善其修复功能的同时增加干细胞在移植微环境中对死亡的适应力。尽管在某些情况下已观察到干细胞分化为心肌细胞，但主要的修复益处是通过旁分泌机制提供的，该机制促进血管生成，细胞存活，转分化宿主细胞并调节免疫反应。通过物理，遗传和药理学方法对干细胞进行离体操作已显示出使细胞在缺血后移植微环境中壮成长的希望。在当前的工作中，我们将概述缺血性心脏病干细胞治疗的现状，讨论使用最多的复发细胞群体，干细胞提供治疗益处的机制以及已用于优化和增加生存率的策略。干细胞的功能，包括用药物和新型“药物优化剂”进行的体外预处理以及遗传修饰。