Understanding exosomes: A history of EV-erything.

BACKGROUND: Extracellular vesicles (EVs), including exosomes, have emerged as fundamental regulators of cell-to-cell communication and are increasingly recognized for their therapeutic and diagnostic promise. While EV research has expanded remarkably over the past two decades, the discipline is rooted in a much longer history of observations, conceptual progress, and technological innovations that gradually transformed the comprehension of these nanosized particles. This review offers a historical perspective on the evolution of EV biology, underscoring the pivotal discoveries, researchers, and community-mediated initiatives that have shaped the contemporary domain. METHODS: A narrative review of the literature was conducted to assess major milestones in EV research, from the earlier descriptions of cell-free particulate material to modern progress in EV biology, standardization, and translational medicine. Particular emphasis was placed on landmark investigations that redefined the biological importance of EVs and on the development of international frameworks that enhanced reproducibility and methodological rigor. RESULTS: Early studies characterized EV-like particles as sedimentable plasma components or cellular waste, culminating in Peter Wolf's description of "platelet dust" in 1967. Subsequent research by Crawford, Johnstone, Stahl, Raposo, Ratajczak, and others established EVs as bioactive structures contributing to vesicle biogenesis, antigen presentation, and horizontal gene transfer of genetic information. Progress in particle characterization, molecular profiling, and imaging approaches further demonstrated EVs as intricate carriers of proteins, lipids, metabolites, and nucleic acids capable of mediating diverse physiological and pathological mechanisms. In parallel, the establishment of the International Society for Extracellular Vesicles (ISEV) and the successive MISEV guidelines offered a pivotal foundation for standardization, transparency, and reproducibility across the discipline. CONCLUSION: The history of EV research reflects a remarkable transition from observations of poorly understood extracellular particles to the recognition of EVs as key modulators of biological communication and potential therapeutic systems. As technological capabilities, standardization efforts, and translational applications continue to advance, EVs are poised to play an increasingly important role in the future of precision medicine.