Beyond Blood Clotting: The Many Roles of Platelet-Derived Extracellular Vesicles

Abstract

Platelet-derived extracellular vesicles (pEVs) are emerging as pivotal players in numerous physiological and pathological processes, extending beyond their traditional roles in hemostasis and thrombosis. As one of the most abundant vesicle types in human blood, pEVs transport a diverse array of bioactive molecules, including growth factors, cytokines, and clotting factors, facilitating crucial intercellular communication, immune regulation, and tissue healing. The unique ability of pEVs to traverse tissue barriers and their biocompatibility position them as promising candidates for targeted drug delivery and regenerative medicine applications. Recent studies have underscored their involvement in cancer progression, viral infections, wound healing, osteoarthritis, sepsis, cardiovascular diseases, rheumatoid arthritis, and atherothrombosis. For instance, pEVs promote tumor progression and metastasis, enhance tissue repair, and contribute to thrombo-inflammation in diseases such as COVID-19. Despite their potential, challenges remain, including the need for standardized isolation techniques and a comprehensive understanding of their mechanisms of action. Current research efforts are focused on leveraging pEVs for innovative anti-cancer treatments, advanced drug delivery systems, regenerative therapies, and as biomarkers for disease diagnosis and monitoring. This review highlights the necessity of overcoming technical hurdles, refining isolation methods, and establishing standardized protocols to fully unlock the therapeutic potential of pEVs. By understanding the diverse functions and applications of pEVs, we can advance their use in clinical settings, ultimately revolutionizing treatment strategies across various medical fields and improving patient outcomes.

Keywords: angiogenesis; hemostasis; immune modulation; platelet-derived extracellular vesicles (pEVs); regenerative medicine.

Figure 1

Biogenesis of extracellular vesicles. EVs are membrane-bound particles released by cells, classified into exosomes, microvesicles, and apoptotic bodies based on their origin and size. Exosomes form within multivesicular bodies and are released when these bodies fuse with the plasma membrane. Microvesicles bud directly from the plasma membrane, while apoptotic bodies result from cell fragmentation during apoptosis. EVs contain cellular lipids, proteins, and nucleic acids, reflecting their parent cell’s state and function. Understanding their biogenesis is essential for leveraging EVs in diagnostics and therapeutic applications.

Figure 2

Isolation of platelet-derived extracellular vesicles (pEVs). Various methods are used to isolate pEVs, each with advantages and limitations. Ultracentrifugation is cost-efficient but may damage vesicles, while membrane filtration is expensive. Gel filtration separates based on size, density gradient centrifugation offers reproducibility, and immunoaffinity chromatography is rapid but costly. Polymer-based precipitation is simple but may co-precipitate other molecules, and tangential flow filtration is ideal for clinical applications but complex and costly. The choice of method depends on factors like sample volume, purity requirements, cost, and reproducibility.

Figure 3

Therapeutic potential of pEVs. pEVs have therapeutic potential in cancer, wound healing, osteoarthritis, sepsis, and cardiovascular diseases through various mechanisms.