Sechenov Institute of Evolutionary Physiology and Biochemistry, The Group of Cytoanalysis, Russian Academy of Sciences, St. Petersburg, Russia.
Almazov National Medical Research Centre, Institute of Experimental Medicine, St. Petersburg, Russia.
Biomed Res Int. 2020 Mar 3;2020:7874109. doi: 10.1155/2020/7874109. eCollection 2020.
Stem cell-based therapy has been considered as a promising option in the treatment of ischemic heart disease. Although stem cell administration resulted in the temporary improvement of myocardial contractility in the majority of studies, the formation of new cardiomyocytes within the injured myocardium has not been conclusively demonstrated. Consequently, the focus of research in the field has since shifted to stem cell-derived paracrine factors, including cytokines, growth factors, mRNA, and miRNA. Notably, both mRNA and miRNA can enter into the extracellular space either in soluble form or packed into membrane vesicles. Stem cell-derived paracrine factors have been shown to suppress inflammation and apoptosis, stimulate angiogenesis, and amplify the proliferation and differentiation of resident cardiac stem cells (CSCs). Such features have led to exosomes being considered as potential drug candidates affording myocardial regeneration. The search for chemical signals capable of stimulating cardiomyogenesis is ongoing despite continuous debates regarding the ability of mature cardiomyocytes to divide or dedifferentiate, transdifferentiation of other cells into cardiomyocytes, and the ability of CSCs to differentiate into cardiomyocytes. Future research is aimed at identifying novel cell candidates capable of differentiating into cardiomyocytes. The observation that CSCs can undergo intracellular development with the formation of "cell-in-cell structure" and subsequent release of transitory amplifying cells with the capacity to differentiate into cardiomyocytes may provide clues for stimulating regenerative cardiomyogenesis.
基于干细胞的治疗方法被认为是治疗缺血性心脏病的一种有前途的选择。尽管在大多数研究中，干细胞给药导致心肌收缩力暂时改善，但在受损心肌内形成新的心肌细胞尚未得到明确证实。因此，该领域的研究重点已转向干细胞衍生的旁分泌因子，包括细胞因子、生长因子、mRNA 和 miRNA。值得注意的是，mRNA 和 miRNA 都可以以可溶性形式或包裹在膜泡中进入细胞外空间。研究表明，干细胞衍生的旁分泌因子可抑制炎症和细胞凋亡，刺激血管生成，并扩增驻留的心脏干细胞（CSC）的增殖和分化。这些特性使得外泌体被认为是提供心肌再生的潜在药物候选物。尽管关于成熟心肌细胞分裂或去分化、其他细胞转分化为心肌细胞的能力以及 CSC 分化为心肌细胞的能力存在持续争论，但寻找能够刺激心肌发生的化学信号的研究仍在继续。未来的研究旨在确定能够分化为心肌细胞的新型候选细胞。观察到 CSC 可以通过形成“细胞内细胞结构”进行细胞内发育，并随后释放具有分化为心肌细胞能力的短暂扩增细胞，这可能为刺激再生性心肌发生提供线索。
