Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
J Cardiol. 2018 Dec;72(6):445-448. doi: 10.1016/j.jjcc.2018.05.002. Epub 2018 Aug 29.
Although cell therapy using myoblasts, bone marrow cells, or other stem cells appears to improve functional recovery of the failing heart, mainly by cytokine paracrine effects, its effectiveness in severely damaged myocardium is limited, probably because there are too few residual myocytes to promote cytokine-induced angiogenesis. Recently, cardiogenic stem cells, such as c-kit-positive cells, were reported to generate cardiomyogenic lineages, and basic research experiments showed that implanting these cells, which can differentiate into cardiomyocytes, improves heart function. However, this functional recovery may have also mainly depended on cytokine paracrine effects, because the differentiation to cardiomyocytes in vivo was poor. In contrast, while Induced Pluripotent Stem Cell-derived cardiomyocytes have paracrine effects, they also have the potential to supply newly born myocytes that can function synchronously with the recipient myocardium as "mechanically working cells" in severely damaged myocardium. Thus, they could represent a "true" myocardial regeneration therapy that can actually regenerate severely damaged myocardium. In addition, iPS cells, especially disease-specific iPS cells, have other applications in regenerative medicine such as in drug screening. In this report, we present the state of basic research in the field of cardiac iPS cells.
虽然使用成肌细胞、骨髓细胞或其他干细胞的细胞治疗似乎通过细胞因子旁分泌作用改善衰竭心脏的功能恢复,但在严重受损的心肌中其效果有限,可能是因为剩余的肌细胞太少,无法促进细胞因子诱导的血管生成。最近,报道了心脏干细胞(如 c-kit 阳性细胞)可产生心肌细胞谱系,基础研究实验表明,植入这些可分化为心肌细胞的细胞可改善心脏功能。然而,这种功能恢复可能主要依赖于细胞因子旁分泌作用,因为体内向心肌细胞的分化较差。相比之下,虽然诱导多能干细胞衍生的心肌细胞具有旁分泌作用,但它们也有可能为严重受损的心肌提供新的、可与受体心肌同步发挥功能的“机械工作细胞”。因此,它们可能代表一种真正的心肌再生治疗方法,实际上可以再生严重受损的心肌。此外,iPS 细胞,特别是疾病特异性 iPS 细胞,在再生医学的其他应用,如药物筛选方面具有其他应用。在本报告中,我们介绍了心脏 iPS 细胞领域的基础研究现状。