Sharma Arun, Zhang Yuan, Wu Sean M
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, 94305, USA,
Curr Treat Options Cardiovasc Med. 2015 Oct;17(10):404. doi: 10.1007/s11936-015-0404-z.
Adult human cardiomyocytes are terminally differentiated and have limited capacity for cell division. Hence, they are not naturally replaced following ischemic injury to the heart. As such, cardiac function is often permanently compromised after an event such as myocardial infarction. In recent years, investigators have focused intensively on ways to reactivate cardiomyocyte mitotic activity in both in vitro cell culture systems and in vivo animal models. In parallel, advances in stem cell biology have allowed for the mass production of patient-specific human cardiomyocytes from human-induced pluripotent stem cells. These cells can be produced via chemically defined differentiation of human pluripotent stem cells in a matter of weeks and could theoretically be utilized directly for therapeutic purposes to replace damaged myocardium. However, stem cell-derived cardiomyocytes, like their adult counterparts, are post-mitotic and incapable of large-scale expansion after reaching a certain stage of in vitro differentiation. Due to this shared characteristic, these stem cell-derived cardiomyocytes may provide a platform for studying genes, pathways, and small molecules that induce cell cycle reentry and proliferation of human cardiomyocytes. Ultimately, the discovery of novel mechanisms or pathways to induce human cardiomyocyte proliferation should improve our ability to regenerate adult cardiomyocytes and help restore cardiac function following injury.
成年人类心肌细胞是终末分化的，细胞分裂能力有限。因此，在心脏缺血性损伤后，它们不会自然更新。这样一来，在诸如心肌梗死等事件后，心脏功能常常会受到永久性损害。近年来，研究人员集中精力探索在体外细胞培养系统和体内动物模型中重新激活心肌细胞有丝分裂活性的方法。与此同时，干细胞生物学的进展使得从人诱导多能干细胞大量生产患者特异性的人类心肌细胞成为可能。这些细胞可以通过对人多能干细胞进行化学定义的分化在数周内产生，理论上可直接用于治疗目的以替代受损的心肌。然而，干细胞衍生的心肌细胞与其成年对应细胞一样，在有丝分裂后，在达到体外分化的某个阶段后无法大规模扩增。由于这一共同特征，这些干细胞衍生的心肌细胞可能为研究诱导人类心肌细胞重新进入细胞周期并增殖的基因、信号通路和小分子提供一个平台。最终，发现诱导人类心肌细胞增殖的新机制或信号通路应能提高我们再生成年心肌细胞的能力，并有助于在损伤后恢复心脏功能。
