Stem-Cell-Derived Extracellular Vesicles as Cargo for Biomolecules including Lipids, Proteins or RNA

Dear Colleagues,

In addition to the conventional molecular secretome, cells secrete large amounts of extracellular vesicles (EVs). EV is “the generic term for a particle naturally released from the cell that is delimited by a lipid bilayer and cannot replicate, i.e. does not contain a functional nucleus” as endorsed by the International Society for Extracellular Vesicles (ISEV). EVs are known to be instruments of intercellular communication to exchange components between cells in normal homeostatic processes, and to contribute to pathological developments.  Stem cells including iPS cells, neural crest cells, and MSCs produce different types of EVs that may have distinct structural and biochemical properties depending on the cell source and intracellular site of origin. Based on the current knowledge of their biogenesis, EVs are broadly divided into two main categories: microvesicles and exosomes. Microvesicles are generated by the outward budding and fission of the plasma membrane and their subsequent release into the extracellular space. They usually comprise vesicles in the size range of 100–1000 nm. Exosomes are formed by the inward budding of the endosomal membrane during the maturation of multivesicular endosomes (MVE) and are secreted upon the fusion of MVE with the cell surface and their size is in the 50 to 150 nm range. Given the limitation in our ability to segregate EV subtypes by isolation techniques, the nomenclature proposed by ISEV uses the terms small EVs and large EVs for vesicles with a diameter lower or higher than 120–150 nm, respectively. Finally, molecules that constitute the EV cargoes are enriched in the forming vesicles by mechanisms of clustering and budding, followed by membrane scission for EV release. The nature and abundance of EV cargoes are cell-type-specific and often influenced by the physiological or pathological state of the parental cell, the stimuli that modulate their release, and the molecular machinery that leads to EV formation. However, a conserved range of proteins are found to be enriched in EVs compared to their parental cells, and EV cargo includes the tetraspanins, heat shock proteins, specific lipids such as phosphatidylserine (PS), sphingomyelin, RNAs (e.g., intact and fragmented messenger RNA, microRNA, transfer RNA, ribosomal RNA fragments, and long non-coding RNA).

Dr. Mangesh Dattu Hade
Prof. Dr. Christian Jorgensen
Dr. Andreina Schoeberlein
Guest Editors

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