18.9:
Overview of Exosomes
Exosomes are vesicles released extracellularly by eukaryotic cells when a multivesicular body fuses with the plasma membrane. They range from 40 to 160 nanometers in diameter.
When released, exosomes send signals to other cells to induce specific responses. They maintain cellular homeostasis, elicit immune responses, and promote or prevent diseases, depending on their tissue of origin and the molecules they contain.
Exosomes may contain a variety of molecules, such as proteins, nucleic acids, lipids, or metabolites. For example, leukocyte-derived exosomes contain interferon-alpha, which prevents viral infection by suppressing the multiplication of the virus.
Since exosomes are intercellular communicators displaying a wide range of functions, they are being explored as therapeutic agents to deliver molecules to specific cellular targets.
Exosomes are also found in body fluids, including plasma, amniotic fluid, semen, and urine. Body-fluid-derived exosomes may contain biomarkers for specific diseases and are being investigated as potential diagnostic agents.
For example, a biomarker for Alzheimer's disease is present at high levels in the exosomes derived from cerebrospinal fluids of affected patients.
18.9:
Overview of Exosomes
Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the plasma membrane. Only after 1983 was it experimentally demonstrated that exosomes are intraluminal vesicles released after multivesicular bodies fuse with the plasma membrane. The term 'exosome' was coined by Johnstone et al. in 1987.
Exosomes can be classified into several categories based on their size, contents, functions, and source. Exosomes contain diverse molecules, including nucleic acids, proteins, lipids, and metabolites, and the functions of exosomes largely depend on their contents. For example, exosomes containing interferons can prevent hepatitis B or HIV infections. In contrast, specific proteins on the exosomal membranes, such as tetraspanins, may allow viruses to enter host cells. Such exosomes may promote a viral infection rather than prevent it.
Exosomes as Diagnostic Tools
Proteins and nucleic acids present in exosomes are being explored for their use as biomarkers. The protein CD81 is present at high levels in exosomal membranes from patients with a hepatitis C infection. Similarly, the microRNAs miR-141 and miR-375 are present at elevated levels in the serum exosomes of patients with prostate cancer.
An online database keeps an up-to-date compilation of the molecules identified in exosomes from both published and unpublished studies. It can be accessed through the ExoCarta website (http://www. exocarta.org). ExoCarta has enabled the identification of conserved proteins, nucleic acids, and other exosomal markers, especially biomarkers for diseases.
Suggested Reading
- Edgar, J. R. (2016). Q&A: What are exosomes, exactly?. BMC biology, 14(1), 1-7.
- Lin, J., Li, J., Huang, B., Liu, J., Chen, X., Chen, X. M., … & Wang, X. Z. (2015). Exosomes: novel biomarkers for clinical diagnosis. The scientific world journal, 2015.
- Simpson, R. J., Kalra, H., & Mathivanan, S. (2012). ExoCarta as a resource for exosomal research. Journal of extracellular vesicles, 1(1), 18374.