Objective:

To establish a molecular reference framework for human circulating extracellular vesicles (EVs) and enhance their clinical utility by improving the understanding of their composition and function.

Key Findings:

• Identified a conserved set of 182 proteins and 52 lipids intrinsic to circulating EVs, which may serve as potential biomarkers.
• Established a panel of 29 proteins and 114 lipids that are non-EV features in plasma, aiding in the differentiation of EVs.
• Developed markers (e.g., ADAM10 and PS(36:1)) for precise differentiation between EV and non-EV particles, which could improve diagnostic accuracy.

Interpretation:

The findings provide a comprehensive molecular profile of human EVs, enhancing their potential as biomarkers in clinical settings and improving the understanding of their role in intercellular communication, which may lead to novel therapeutic strategies.

Limitations:

• The complexity of plasma makes it challenging to isolate EVs without contamination, potentially affecting the reliability of the findings.
• Conventional EV markers are inconsistent for reliable separation from other plasma components, which may limit the applicability of the results.

Conclusion:

This study lays the groundwork for future EV research, enabling the development of diagnostic tools and therapeutic strategies based on the molecular identity of EVs, ultimately aiming to improve patient outcomes.