Therapeutic efficacy of the mesenchymal stromal cell (MSC), a multipotent progenitor cell, is attributed to small (50 to 200 nm) extracellular vesicles (EVs). The presence of a lipid membrane differentiates exosomes and EVs from other macromolecules. Analysis of this lipid membrane revealed three distinct small MSC EV subtypes each with a differential affinity for cholera toxin B chain (CTB), annexin V (AV), and shiga toxin B chain (ST) that binds GM1 ganglioside, phosphatidylserine, and globotriaosylceramide, respectively. Similar EV subtypes are also found in biologic fluids and are independent sources of disease biomarkers.
Here, researchers from the Institute of Medical Biology, Singapore compared and contrasted these three EV subtypes. All subtypes carry β-actin, but only CTB-binding EVs (CTB-EVs) are true exosomes, enriched with exosome proteins and derived from endosomes. No unique protein has been identified yet in AV-binding EVs (AV-EVs); ST-binding EVs (ST-EVs) carry RNA and a high level of extra domain A (EDA)-containing fibronectin. Based on the CTB, AV, and ST subcellular binding sites, the origins of CTB-, AV- and ST-EV biogenesis are the plasma membrane, cytoplasm, and nucleus, respectively. The differentiation of EV subtypes through membrane lipids underlies the importance of membrane lipids in defining EVs and implies an influence on EV biology and functions.