Comparison of serum and plasma as a source of blood extracellular vesicles: Increased levels of platelet-derived particles in serum extracellular vesicle fractions alter content profiles from plasma extracellular vesicle fractions

PLoS One. 2022 Jun 24;17(6):e0270634. doi: 10.1371/journal.pone.0270634. eCollection 2022.


Extracellular vesicles (EVs) have attracted much attention as potential diagnostic biomarkers for human diseases. Although both plasma and serum are utilized as a source of blood EVs, it remains unclear whether, how and to what extent the choice of plasma and serum affects the experimental results. To address this issue, in this study, we performed comprehensive characterization of EV fractions derived from plasma and serum, and investigated the differences between these blood EVs. We demonstrated by nanoparticle tracking analysis that EV fractions derived from serum contain more particles than those from plasma of mice. Proteomic analysis demonstrated that platelet-associated proteins are selectively enriched in serum EV fractions from both mice and humans. A literature review of proteomic data of human blood EVs reported by other groups further confirmed that selective enrichment of platelet-associated proteins is commonly observed in serum EVs, and confers different proteome profiles to plasma EVs. Our data provide experimental evidence that EV fractions derived from serum generally contain additional EVs that are released from platelets, which may qualitatively and quantitatively alter EV profiles when using serum as a source of blood EVs.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets
  • Extracellular Vesicles* / metabolism
  • Mice
  • Plasma
  • Proteomics* / methods

Grant support

This work was supported by Grants-in-Aid for Scientific Research (B) (18H02585 to TT; 16H05325 to YN) from the Japan Society for the Promotion of Science (JSPS), Japan; by a grant from Precursory Research for Embryonic Science and Technology (PRESTO) of the Japan Science and Technology Agency (JST) (JPMJPR17H8 to TT); by Research and Development Grants for Dementia (JP18dk0207030 and JP21dk0207042 to Y.N.) from the Japan Agency for Medical Research and Development; and by grants from the Human Frontier Science Program (RGY0066/2017), the Uehara Memorial Foundation, Nakatani Foundation, the Tokyo Biochemical Research Foundation, the Asahi Glass Foundation, Mochida Memorial Foundation, the Nakatomi Foundation (to TT).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.