The new composition of circulating microvesicles: optimized protocols and reassessment of their characteristics and physiological functions

Circulating microvesicles (MVs), a subset of extracellular vesicles, play vital roles in intercellular communication and hold great promise as biomarkers for metabolic, cardiovascular, and malignant diseases. However, inconsistencies in their isolation protocols have long obscured their biological identity and function.

In a groundbreaking study titled “The New Composition of Circulating Microvesicles: Optimized Protocols and Reassessment of Their Characteristics and Physiological Functions,” Professor Guorui Huang and his colleagues from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine systematically compared MVs isolated at different centrifugal speeds and uncovered a pivotal insight: 3000 g is the critical boundary that defines genuine MVs.

The team found that over 80% of the particles obtained under traditional protocols (≤1500 g) originate from platelets or platelet fragments, whereas centrifugation at ≥3000 g significantly reduces this contamination, yielding a stable population of true cell-derived MVs. Using confocal microscopy, flow cytometry, dynamic light scattering, and transmission electron microscopy, the researchers confirmed that the optimized protocol produces MVs with uniform morphology (100–500 nm) and consistent cellular origins.

Functionally, the findings redefine long-standing assumptions in the field. Contrary to previous reports attributing procoagulant activity to MVs, this study demonstrated that such effects belong to platelet granules, not true MVs. Instead, MVs isolated using the improved method exhibited anti-inflammatory, pro-angiogenic, and endothelial-protective properties, while also suppressing tumor cell proliferation and migration. These discoveries establish a new foundation for accurately interpreting MVs’ physiological and pathological functions.

“Our work redefines the starting point of microvesicle research,” said Professor Huang. “By optimizing the isolation protocol, we can now study the genuine MVs and their biological roles without platelet interference. This breakthrough will standardize the field and accelerate the translational use of MVs in disease diagnosis and therapy.”

This research not only provides a methodological benchmark for future extracellular vesicle studies but also opens new directions for exploring MVs as biomarkers and therapeutic targets in cardiovascular, inflammatory, and metabolic disorders.