School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China.
Cells. 2021 Sep 18;10(9):2463. doi: 10.3390/cells10092463.
Pluripotent stem cells (PSCs) can undergo unlimited self-renewal and can differentiate into all the cell types present in our body, including cardiomyocytes. Therefore, PSCs can be an excellent source of cardiomyocytes for future regenerative medicine and medical research studies. However, cardiomyocytes obtained from PSC differentiation culture are regarded as immature structurally, electrophysiologically, metabolically, and functionally. Mitochondria are organelles responsible for various cellular functions such as energy metabolism, different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Cells can respond to cellular needs to increase the mitochondrial mass by mitochondrial biogenesis. On the other hand, cells can also degrade mitochondria through mitophagy. Mitochondria are also dynamic organelles that undergo continuous fusion and fission events. In this review, we aim to summarize previous findings on the changes of mitochondrial biogenesis, mitophagy, and mitochondrial dynamics during the maturation of cardiomyocytes. In addition, we intend to summarize whether changes in these processes would affect the maturation of cardiomyocytes. Lastly, we aim to discuss unanswered questions in the field and to provide insights for the possible strategies of enhancing the maturation of PSC-derived cardiomyocytes.
多能干细胞(PSCs)可以进行无限自我更新,并能分化为我们体内存在的所有细胞类型,包括心肌细胞。因此,PSCs 可以成为未来再生医学和医学研究的理想心肌细胞来源。然而,从 PSC 分化培养中获得的心肌细胞在结构、电生理、代谢和功能上都被认为是不成熟的。线粒体是负责多种细胞功能的细胞器,如能量代谢、不同的分解代谢和合成代谢过程、钙通量和各种信号通路。细胞可以通过线粒体生物发生来响应细胞的需求增加线粒体质量。另一方面,细胞也可以通过自噬来降解线粒体。线粒体也是动态细胞器,经历持续的融合和裂变事件。在这篇综述中,我们旨在总结以前关于心肌细胞成熟过程中线粒体生物发生、自噬和线粒体动力学变化的研究结果。此外,我们还旨在总结这些过程的变化是否会影响心肌细胞的成熟。最后,我们旨在讨论该领域尚未解决的问题,并为增强 PSC 衍生的心肌细胞成熟提供可能的策略的见解。