Abstract
The therapeutic efficacy of mesenchymal stromal cells (MSCs), multipotent progenitor cells, is attributed to small (50-200 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 bind GM1 ganglioside, phosphatidylserine, and globotriaosylceramide, respectively. Similar EV subtypes are also found in biologic fluids and are independent sources of disease biomarkers. Here, we compare and contrast 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-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.
Highlights
The therapeutic efficacy of mesenchymal stromal cells (MSCs), multipotent progenitor cells, is attributed to small (50–200 nm) extracellular vesicles (EVs)
The lipid membrane of an EV defines and limits the physical structure of the EV, it is integral to EV biogenesis and cargo loading
Differences in the membrane lipid composition of sized EVs can denote a difference in biogenesis, cargo content, and functions
Summary
MSC exosomes were first described in 2010 [3]. They are presently classified as a member of the family of small EVs that comprises secreted lipid membrane vesicles of 50–200 nm. Apart from having a much wider size range, this microvesicle preparation has several other features that contrast significantly with those in the exosome preparation This preparation contains mRNA, and mammalian RNAs have an estimated median length of 1.4 kb [11]. The presence of a proteome enriched in proteins associated with endocytosis, endosome-associated activities, or exocytosis, and the colocalization of endocytosed transferrin and CTB with exosome markers confirmed that CTB-EVs from MSCs are bona fide exosomes. This association between CTB and exosomes was further confirmed recently when cholera toxin was shown to be propagated from cell to cell through exosomes [23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
