Graduate Student Yonsei University College of Medicine, Republic of Korea
Abstract: Given the heart's inherent inability to regenerate, cardiovascular diseases remain a formidable challenge due to the limited regenerative potential of native cardiac tissue. Small-molecule-based direct cardiac reprogramming has emerged as a promising strategy for cardiac regeneration, offering a rapid and non-invasive alternative to genetic modification. However, clinical translation of this approach is hindered by obstacles such as low reprogramming efficiency and functional immaturity of the reprogrammed cells.
This study investigates the role of mitochondria delivery in enhancing the metabolic activity and maturation of chemically induced cardiomyocyte-like cells (CiCMs). By leveraging mitochondria from high-energy organs (heart, brain, liver), we achieved significant improvements in structural and metabolic maturation. Notably, heart-mitochondria(h-mito) induced CiCMs to exhibit elevated oxygen consumption rates, improved electrophysiological properties, and heightened sensitivity to hypoxic stress. These functional advancements are attributed to metabolic reprogramming driven by enhanced protein internalization and increased bioenergetic activity in CiCMs.
In conclusion, our findings underscore the potential of h-mito delivery to markedly enhance the metabolic activity and maturation of CiCMs, thereby advancing their applicability in regenerative medicine and disease modeling. Furthermore, our results highlight the broader therapeutic implications of tissue-specific mitochondrial transplantation.
Funding Source: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1C1C2009131) and the Brain Korea 21 Project for Medical Science, Yonsei University.
