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Exosomes: The Rising Biotherapy in Cardiac repair

Commented by the ESC WG on Cardiovascular Regenerative & Reparative Medicine

Microvesicles, Exosomes

Extracellular vesicles (EV) and exosomes are increasingly being studied for their role in cell-to-cell communication through bioactive molecules such as RNAs and proteins that modulate immune and regenerative pathways. As demonstrated by several very recent papers, they are emerging as key players in cardiovascular medicine, for both diagnosis and treatment of myocardial infarction (Gu et al., 2024; Das et al., 2024). This focus on exosome-based therapies for cardiovascular diseases is now shaping the research landscape for cardiac biotherapies 

EVs and Exosomes, isolated from various cell sources, enhance myocardial repair by modulating multiple tissue repair pathways and promoting angiogenesis. Recent studies demonstrated that intracoronary delivery of exosomes derived from human cardiac progenitor cells in a porcine model of MI significantly reduced infarct size and improved heart function (Emmert et al., 2024). Prieto-Vila et al. further validated the effectiveness of EVs derived from adult cardiomyocytes in a mouse MI model, showing that these EVs reduced fibrosis by reversing the activation of fibroblasts and suppressing several signaling pathways, including MAPK, mTOR, JAK/STAT, TGF-β, and PI3K/Akt.

Traditionally, exosomes have been administered intramyocardially, intracoronary or intravenously for MI treatment. However, Li et al. introduced different therapeutic intervention and demonstrated that inhalable stem cell-derived exosome therapy (SCENT) can enhance cardiac repair. SCENT improved heart function, reduced fibrosis, promoted cardiomyocyte proliferation, and downregulated CD36 in endothelial cells in both mouse and swine MI models.

This study positions exosome delivery as a non-invasive and repeatable treatment method. However, challenges remain, particularly in optimizing retention, targeting specific tissues, and identifying the complex mechanisms involved.

References


  1. Das, D., Jothimani, G., Banerjee, A., Dey, A., Duttaroy, A. K., & Pathak, S. (2024). A brief review on recent advances in diagnostic and therapeutic applications of extracellular vesicles in cardiovascular disease. The international journal of biochemistry & cell biology, 173, 106616.
  2. Emmert, M. Y., Burrello, J., Wolint, P., Hilbe, M., Andriolo, G., Balbi, C., Provasi, E., Turchetto, L., Radrizzani, M., Nazari-Shafti, T. Z., Cesarovic, N., Neuber, S., Falk, V., Hoerstrup, S. P., Hemetsberger, R., Gyöngyösi, M., Barile, L., & Vassalli, G. (2024). Intracoronary delivery of extracellular vesicles from human cardiac progenitor cells reduces infarct size in porcine acute myocardial infarction. European heart journal, 45(9), 728–732.
  3. Gu, Y., Feng, J., Shi, J., Xiao, G., Zhang, W., Shao, S., Liu, B., & Guo, H. (2024). Global Research Trends on Exosome in Cardiovascular Diseases: A Bibliometric-Based Visual Analysis. Vascular health and risk management, 20, 377–402.
  4. Li, J., Sun, S., Zhu, D., Mei, X., Lyu, Y., Huang, K., Li, Y., Liu, S., Wang, Z., Hu, S., Lutz, H. J., Popowski, K. D., Dinh, P. C., Butte, A. J., & Cheng, K. (2024). Inhalable Stem Cell Exosomes Promote Heart Repair After Myocardial Infarction. Circulation, 150(9), 710–723.
  5. Prieto-Vila, M., Yoshioka, Y., Kuriyama, N., Okamura, A., Yamamoto, Y., Muranaka, A., & Ochiya, T. (2024). Adult cardiomyocytes-derived EVs for the treatment of cardiac fibrosis. Journal of extracellular vesicles, 13(7), e12461.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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