A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences

Abstract

Platelets have been shown to be associated with pathophysiological process beyond thrombosis, demonstrating critical additional roles in homeostatic processes, such as immune regulation, and vascular remodeling. Platelets themselves can have multiple functional states and can communicate and regulate other cells including immune cells and vascular smooth muscle cells, to serve such diverse functions. Although traditional platelet functional assays are informative and reliable, they are limited in their ability to unravel platelet phenotypic heterogeneity and interactions. Developments in methods such as electron microscopy, flow cytometry, mass spectrometry, and 'omics' studies, have led to new insights. In this Review, we focus on advances in platelet biology and function, with an emphasis on current and promising methodologies. We also discuss technical and biological challenges in platelet investigations. Using coronavirus disease 2019 (COVID-19) as an example, we further describe the translational relevance of these approaches and the possible 'bench-to-bedside' utility in patient diagnosis and care.

Fig. 1 |

Schematic representation of physiological and pathological roles of platelets. Although classically considered as mediators of hemostasis and thrombosis, platelets have been demonstrated to play a wide range of other physiological and pathological roles. Their physiological functions include the maintenance of vascular integrity through interaction with the vascular wall and contributions to wound healing and angiogenesis^,. Platelets also maintain plasma content homeostasis by storing and releasing many essential plasma factors such as growth factors (VEGF, TGF-β, etc.) and vascular tone regulators such as serotonin. Platelets are intricately linked to physiological inflammatory responses through cytokine storage and release and by interacting with diverse circulating immune cells. Many of these homeostatic functions are mediated through transfer to other cells (for example, mRNA or miRNA) or acceptance from other cells. Platelets are well studied for their pathological roles in thrombotic disorders, such as enhanced vascular thrombosis in diabetes mellitus and many other disease processes. Platelets have also been linked to the pathogenesis of disease states such as infections (sepsis and viral infections including COVID-19 (refs. ^–)) and malignancies in addition to inflammatory disorders, autoimmune disorders, liver disease and kidney disease^,. This functional diversity in both physiological and pathological contexts is unusual for a small, short-lived cell with no nucleus. Complementing basic investigations with clinical methodology can provide critical mechanistic insights into these diverse functions. DIC, differential interference contrast.