Depending (without entrance); releasing their content through extracellular

Depending on the cell of origin, exosomes contain specific protein and lipid constituents. Although, most exosomes have similar components due to their endosomal origin. Heat shock proteins, fusion and membrane transporters (annexins, RabGTPases and flotilin), MVBs proteins such as TSG101, Alix, integrins and tetraspanins (CD9, CD63, CD81 and CD82) are common exosomal proteins. Furthermore, special glycosylated motifs enriched with raft-lipids such as sphingolipids, cholesterol and ceramide are typically observed as their lipid component 3.
Exosomes affect target cells through the following mechanisms: activation of certain signaling pathways by ligand-receptor interaction (without entrance); releasing their content through extracellular proteases-mediated cleavage and subsequent binding of contents to cell surface receptors; fusion to the cell membrane and releasing their content into the cytoplasm; entering cells by endocytic mechanisms such as receptor-mediated endocytosis, phagocytosis and macropinocytosis 1,3.
Relative to other cell types, mesenchymal stromal cells (MSCs) possess distinct advantages as exosome source. They release higher amounts of exosome compared to other cells. MSC-derived EVs are relatively well-tolerated in different animal models and show more stability and sustainability in human plasma and at -20 °C. Moreover, MSC-derived exosomes release paracrine mediators and exhibit regenerative properties. As natural nano-vesicles, exosomes are good candidates for drug delivery due to their low immunogenicity and ability to enter tissues and even cross the blood–brain barrier 4. However, exosomes are rapidly cleared by reticulum endothelial system and generally should be specifically targeted against desired cells, thus the clinical usage of these EVs is still a subject of debate.

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