Graduate Student The Chinese University of Hong Kong (CUHK) Hong Kong, Hong Kong
Abstract: Cardiac regenerative medicine has provided promising solutions to cardiac diseases as researchers can now generate cardiomyocytes (CMs) from pluripotent stem cells (PSCs). Nevertheless, the immature state of PSC-derived CMs (PSC-CMs) has become the major difficulty of their utilization. Multifaceted methods, including hormonal induction and tissue engineering, have been used to enhance PSC-CMs’ maturity, but a comprehensive maturation status has not yet been achieved. The perinatal phase has been recognized as a crucial time point for the in vivo maturation of mammalian CMs. Shortly after birth, CMs undergo a short period of starvation which leads to autophagy and mitophagy, ultimately resulting in structural and metabolic alterations. Mitophagy is the selective autophagy of mitochondria; it is a critical process in mediating metabolic transition and is pivotal for the maturation of CMs. Mitophagy in mammalian cells can be divided into two major pathways. One is receptor-mediated mitophagy, the other one is PINK1-Parkin-mediated mitophagy. Notably, Parkin has been shown to be associated with CMs’ maturation. In the current study, starvation and bafilomycin A1 (Baf A1) were used to increase and inhibit mitophagy, respectively, in PSC-CMs. Interestingly, increase in mitophagy in CMs demonstrated an increased in maturity as reflected by multiple parameters, including an increase in calcium transient kinetics, cell size and sarcomere length. On the other hand, Baf A1-treated CMs exhibited a decreased in maturity in various aspects. The preliminary data revealed that mitophagy positively regulates PSC-CMs maturation, however, the underlying pathway of how mitophagy regulates PSC-CMs maturity remains elusive. Further study would be conducted to elucidate this. By understanding how mitophagy contributes to the maturation of CMs, this study aims to delineate an understudied molecular pathway that holds great promise for enhancing PSC-CM maturity.
