Exosome (vesicle)

Exosomes are 30-90 nm vesicles secreted by a wide range of mammalian cell types. First discovered in maturing mammalian reticulocytes, they were shown to be a mechanism for selective removal of many plasma membrane proteins. These proteins are lost or reduced in amount, without concomitant degradation, during the maturation to the erythrocyte. Although the exosomal protein composition varies with the cell of origin, most exosomes contain the soluble protein Hsc 70 and many others. 31 proteins are found to be in common between colorectal cancer, mast cells and urine-derived exosomes. For a list of exosome protein markers that are more often identified in exosomes, see ExoCarta, exosome database. Certain cells of the immune system, such as dendritic cells and B cells, secrete exosomes that many scientists believe play a functional role in mediating adaptive immune responses to pathogens and tumors. Intralumenal endosomal vesicles can become exosomes in case they are released to the extracellular medium.

Exosomes contain both proteins and RNA molecules. An overview of molecules known to be present in exosomes is provided in the ExoCarta database. Most exosomes studied to date have an evolutionary-conserved set of protein molecules and a set of tissue/cell type-specific proteins that distinguishes exosomes secreted by different cell types. Exosome protein cargo could also be modulated by the external microenvironment. For example, tumor cells exposed to hypoxia secrete exosomes with enhanced angiogenic and metastatic potential suggesting that tumor cells adapt to a hypoxic microenvironment by secreting exosomes to stimulate angiogenesis or facilitate metastasis to more favourable environment. On the other hand, myc-immortalization of mesenchymal stem cell did not alter the cardioprotective potency of its secreted exosomes. The RNA molecules in exosomes include mRNA and miRNA, which can be shuttled from one cell to another, affecting the recipient cell's protein production. This RNA is called "exosomal shuttle RNA". Many of the miRNAs in exosomes secreted by mesenchymal stem cells are predominantly pre- and not mature miRNAs. There were no RISC-associated proteins in these exosomes, suggesting that only the pre-miRNAs but not the mature miRNAs in MSC exosomes have the potential to be biologically active in the recipient cells.

Clinical applications
Exosomes from red blood cells contain the transferrin receptor which is absent in mature erythrocytes. Dendritic cell-derived exosomes express MHC I, MHC II, and costimulatory molecules and have been proven to be able to induce and enhance antigen-specific T cell responses in vivo. In addition, the first exosome-based cancer vaccination platforms are being explored in early clinical trials. Exosomes can also be released into urine by the kidneys and their detection might serve as a diagnostic tool. Urinary exosomes may be useful as treatment response markers in prostate cancer. Exosomes released from tumors into the blood can also be used diagnostically. Exosomes carry RNA from the cell it was released from, and J. Skog, et al. were the first to show that tumor mutations in brain tumors can be detected in exosomes from a serum sample, facilitating a blood-based biomarker platform for solid tumors. This technology platform is now being developed by the company Exosome Diagnostics Inc.. A blood-based diagnostic technology, called Carisome™, which captures and characterizes circulating microvesicles, including exosomes, is also being developed by Caris Life Sciences. Studies from Singapore A*STAR Institute of Medical Biology - Exosomes and Secreted Nano-vesicles Research Laboratory have shown for the first time that exosomes secreted by mesenchymal stem cells (MSC) reduce myocardial ischemia/reperfusion injury suggesting a novel exosome-based therapeutic modality for cardiovascular disease