Exosome Biogenesis: Meta-Analysis of Intraluminal Vesicle Size Across Species

Exosomes, a major subpopulation of small extracellular vesicles (sEV), are conserved mediators of intercellular communication, yet the properties of their endosomal precursors, intraluminal vesicles (ILV), have not been systematically quantified across species or imaging modalities. This study systematically evaluates ILV sizes across diverse eukaryotic species and modalities while assessing their relationship to secreted sEV sizes. We carried out two complementary meta-analyses of ILV sizes based on transmission electron microscopy (TEM) and cryogenic electron microscopy (cryo-EM) data across species. This was followed by in situ assessment of sEVs secreted by HEK293T cells with TEM, nanoparticle tracking analysis and super-resolution microscopy characterization. Across species, imaging modalities, and cellular contexts, ILV sizes were under approximately 200 nm, with a mean diameter of 100.5 nm, overlapping with the size range of sEVs. This study addresses an existing knowledge gap by systematically evaluating ILV size across species and revealing an upper size limit of approximately 200 nm.