National Institute of Rheumatic Diseases, Nábrežie I. Krasku 4, 921 12 Piešťany, Slovakia.
Institute of Histology and Embryology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.
Int J Mol Sci. 2022 Sep 7;23(18):10314. doi: 10.3390/ijms231810314.
Because of cardiomyocyte death or dysfunction frequently caused by myocardial infarction (MI), heart failure is a leading cause of morbidity and mortality in modern society. Paradoxically, only limited and non-curative therapies for heart failure or MI are currently available. As a result, over the past two decades research has focused on developing cell-based approaches promoting the regeneration of infarcted tissue. Cell-based therapies for myocardial regeneration include powerful candidates, such as multipotent stem cells (mesenchymal stem cells (MSCs), bone-marrow-derived stem cells, endothelial progenitor cells, and hematopoietic stem cells) and induced pluripotent stem cells (iPSCs). These possess unique properties, such as potency to differentiate into desired cell types, proliferation capacity, and patient specificity. Preclinical and clinical studies have demonstrated modest improvement in the myocardial regeneration and reduced infarcted areas upon transplantation of pluripotent or multipotent stem cells. Another cell population that need to be considered as a potential source for cardiac regeneration are telocytes found in different organs, including the heart. Their therapeutic effect has been studied in various heart pathologies, such as MI, arrhythmias, or atrial amyloidosis. The most recent cell-free therapeutic tool relies on the cardioprotective effect of complex cargo carried by small membrane-bound vesicles-exosomes-released from stem cells via exocytosis. The MSC/iPSC-derived exosomes could be considered a novel exosome-based therapy for cardiovascular diseases thanks to their unique content. There are also other cell-free approaches, e.g., gene therapy, or acellular cardiac patches. Therefore, our review provides the most recent insights into the novel strategies for myocardial repair based on the regenerative potential of different cell types and cell-free approaches.
由于心肌梗死 (MI) 经常导致心肌细胞死亡或功能障碍,心力衰竭是现代社会发病率和死亡率的主要原因。矛盾的是,目前仅有限的、非治愈性的心力衰竭或 MI 治疗方法可用。因此,在过去的二十年中,研究的重点是开发促进梗死组织再生的基于细胞的方法。用于心肌再生的细胞疗法包括有前途的候选物,如多能干细胞(间充质干细胞 (MSCs)、骨髓源性干细胞、内皮祖细胞和造血干细胞)和诱导多能干细胞 (iPSCs)。这些细胞具有独特的特性,如分化为所需细胞类型的能力、增殖能力和患者特异性。临床前和临床研究表明,在移植多能或多能干细胞后,心肌再生和减少梗死面积有适度改善。另一种需要考虑作为心脏再生潜在来源的细胞群体是存在于不同器官(包括心脏)中的 telocytes。它们的治疗效果已在各种心脏病理中进行了研究,例如 MI、心律失常或心房淀粉样变性。最近的无细胞治疗工具依赖于通过胞吐作用从小而膜结合的囊泡(外泌体)中释放的干细胞携带的复杂货物的心脏保护作用。MSC/iPSC 衍生的外泌体由于其独特的内容,可被视为一种新型基于外泌体的心血管疾病治疗方法。还有其他无细胞方法,例如基因治疗或去细胞心脏贴片。因此,我们的综述提供了基于不同细胞类型和无细胞方法的再生潜力的心肌修复的最新见解。