Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia; Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.
Clin Ther. 2020 Oct;42(10):1880-1891. doi: 10.1016/j.clinthera.2020.08.010. Epub 2020 Sep 13.
Cardiac pathologies remain a dominant cause of morbidity and mortality within the community. The drive to develop therapies capable of repairing damaged heart tissue to achieve clinically significant restoration of function has motivated the pursuit of novel approaches such as cell therapy. To this end, evidence of therapeutic benefits achieved by using mesenchymal stem cells (MSCs) has captured considerable interest despite a relative lack of information regarding the mechanisms involved. This narrative review synthesizes and interprets the current literature describing mechanisms by which MSCs can elicit cardiac repair, thereby directing attention to avenues of further inquiry.
OVID versions of MEDLINE and EMBASE were searched for studies describing the role of MSCs in mammalian cardiac repair. Additional studies were sourced from the reference lists of relevant articles and other personal files.
MSCs elicit cardiac repair in a range of in vitro systems and animal models of diseases such as myocardial infarction and heart failure. Important mechanisms include the preservation of myocardial contractility, the promotion of angiogenesis, and the modulation of fibrosis. Exposing in vitro MSCs to a microenvironment reflective of that encountered in the injured heart seems to potentiate these therapeutic mechanisms.
Promising results in animal studies warrant continuation of clinical MSC cardiac therapy studies. Paracrine functions of MSCs seem to be the dominant mechanism of cardiac repair over direct cellular effects. Although integral, the MSC secretome remains poorly defined. In addition, most of the mechanistic data within the literature have been derived from animal MSC research, necessitating more human MSC-based work.
心脏病理学仍然是社区中发病率和死亡率的主要原因。开发能够修复受损心脏组织以实现临床显著功能恢复的治疗方法的动力，促使人们寻求新的方法，如细胞疗法。为此，尽管关于涉及的机制的信息相对较少，但使用间充质干细胞（MSCs）实现治疗益处的证据引起了相当大的兴趣。本叙述性评论综合并解释了目前描述 MSCs 如何引发心脏修复的文献，从而将注意力引向进一步探究的途径。
在 OVID 版本的 MEDLINE 和 EMBASE 中搜索描述 MSCs 在哺乳动物心脏修复中的作用的研究。还从相关文章的参考文献列表和其他个人文件中获取了其他研究。
MSCs 在多种体外系统和疾病动物模型（如心肌梗死和心力衰竭）中引发心脏修复。重要的机制包括心肌收缩力的保持、血管生成的促进和纤维化的调节。将体外 MSC 暴露于类似于受伤心脏中遇到的微环境似乎会增强这些治疗机制。
动物研究中的有希望的结果证明继续进行 MSC 心脏治疗的临床研究是合理的。MSCs 的旁分泌功能似乎是心脏修复的主要机制，而不是直接的细胞作用。尽管必不可少，但 MSC 分泌组仍未得到很好的定义。此外，文献中的大多数机制数据都来自于动物 MSC 研究，因此需要更多基于人类 MSC 的工作。
