Exosome (vesicle)
Encyclopedia
Exosomes are 30-90 nm vesicles
secreted by a wide range of mammal
ian cell types. First discovered in maturing mammalian reticulocyte
s, 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 tumor
s. 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.
s 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
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
secreted by a wide range of mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian cell types. First discovered in maturing mammalian reticulocyte
Reticulocyte
Reticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body.Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells,...
s, 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
Hsc70
Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene.- Function :...
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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, 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 tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s. 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
Mesenchymal stem cell
Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts , chondrocytes and adipocytes...
did not alter the cardioprotective potency of its secreted exosomes. The RNA molecules in exosomes include mRNA and miRNA
Mirna
Mirna may refer to:geographical entities* Mirna , a river in Istria, Croatia* Mirna , a river in Slovenia, tributary of the river Sava* Mirna , a settlement in the municipality of Mirna in Southeastern Sloveniapeople...
, 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 cellRed blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s contain the transferrin receptor
Transferrin receptor
Transferrin receptor is a carrier protein for transferrin. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration...
which is absent in mature erythrocytes. Dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
-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
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
responses in vivo. In addition, the first exosome-based cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
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
External links
- http://www.exocarta.org ExoCarta—A database of molecules identified in exosomes.
- http://www.exosome.com Exosome.com—A resource on the advances in exosome technology
- http://www.carislifesciences.com/microvesicle-technology-carisome Carisome Diagnostic Techology