Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults

Abstract

Exosomes are extracellular vesicles that contain nucleic acids, lipids and metabolites, and play a critical role in health and disease as mediators of intercellular communication. The majority of extracellular vesicles in the blood are platelet-derived. Compared to adults, neonatal platelets are hyporeactive and show impaired granule release, associated with defects in Soluble N-ethylmaleimide-sensitive fusion Attachment protein REceptor (SNARE) proteins. Since these proteins participate in biogenesis of exosomes, we investigated the potential differences between newborn and adult plasma-derived exosomes. Plasma-derived exosomes were isolated by ultracentrifugation of umbilical cord blood from full-term neonates or peripheral blood from adults. Exosome characterization included size determination by transmission electron microscopy and quantitative proteomic analysis. Plasma-derived exosomes from neonates were significantly smaller and contained 65% less protein than those from adults. Remarkably, 131 proteins were found to be differentially expressed, 83 overexpressed and 48 underexpressed in neonatal (vs. adult) exosomes. Whereas the upregulated proteins in plasma exosomes from neonates are associated with platelet activation, coagulation and granule secretion, most of the underexpressed proteins are immunoglobulins. This is the first study showing that exosome size and content change with age. Our findings may contribute to elucidating the potential “developmental hemostatic mismatch risk” associated with transfusions containing plasma exosomes from adults.

Platelets in pediatric and neonatal sepsis: novel mediators of the inflammatory cascade

“…126 A recent paper showed that neonatal EVs from umbilical cord blood are different in size, concentration and in their protein content from adult EVs, with an increased expression of prothrombotic proteins and a lower expression of immunoglobulins. 127 This supports previous work from our group examining size and concentration of neonatal EVs and how this alters in the first 3 days in premature infants. 128 In addition to EVs, degranulation is associated with the release of a range of proteins termed the platelet releasate.…”

Stem Cell-Derived Nanovesicles: A Novel Cell-Free Therapy for Wound Healing

“…Studies have revealed that the main therapeutic effect of platelets during bleeding is dependent on the effect of platelet-derived extracellular vesicles [ 28 ]. Neonatal plasma exosomes can be enriched in a large number of proteins involved in platelet function and primary hemostasis, such as platelet activation and signaling proteins, integrins α IIb and β 3, platelet chemotactic protein (PF4), filaggrin-A, and ligand receptor (CD36) [ 29 ]. The use of platelet exosomes shows the advantage of the hemostatic effect over fresh platelets [ 30 ].…”

Hypoxic bone marrow mesenchymal stromal cells‐derived exosomal miR ‐182‐5p promotes liver regeneration via FOXO1 ‐mediated macrophage polarization

“…[20][21][22] Among them, exosomes (Exo) are a group of extracellular vesicles with diameters ranging from 30 to 160 nm. 23,24 Exo are thought to functionally mediate cell-to-cell communication by transferring diverse bioactive substances such as proteins, mRNA, and small non-coding RNAs. 25,26 Previous studies demonstrated that MSC-Exo could mimic the capabilities of MSCs to enhance recovery in animal models of liver injury and liver regeneration.…”