Traditionally, exosomes were thought to be no more than “cellular rubbish bags”, that discard unwanted proteins. The interest in exosomes is an increasing field of research with growing potential for many applications. A blog written by Dima Ter-Ovanesyan, labels exosomes as ”the little vesicle that could”, which is fitting when considering that these sub-microscale vesicles had their first conference in 2011 [1].

As always, Charles Darwin was the first to describe the budding of small particles from cell membranes in 1868 [2]. In the 1980’s, exosomes were first imaged using an electron microscope [3]. It was twenty years later that interest in exosomes intensified. It was discovered that not only did exosomes contain proteins but also RNA [4-6]. These RNA delivery systems have created huge potential in many therapeutic and disease diagnosis applications.
Potential applications include the use of biomarkers and using the RNA “signatures” for specific diseases. As exosomes are found in urine, blood and saliva, new diagnostic tools are endless.

In the past decade, research has already found interesting applications.

• It was found that mRNA isolated from exosomes in blood can be used to classify brain tumours.
• A specific mRNA isolated from exosomes in cerebrospinal fluid was found in brain trauma patients but not in healthy controls.
• Also mRNA isolated from exosomes in the blood of pregnant women could be used to predict premature births.
• They have also strong evidence for use as drug delivery systems due to their high biocompatibility[7].

Locally, Dr Michael Michael from The Flinders Centre for Innovation in Cancer is investigating the use of exosomes as biomarkers for cancer diagnosis and works in close collaboration with Dr Jonathan Gleadle who is researching urine exosomes as biomarkers for kidney disease and hypoxia.

With the ever growing potential with these small nanosized vesicle, it is no surprise that researchers are getting on board the “little vesicle that could” train.

Figure 1.  a)Electron micrograph of negatively stained urinary exosomes (scale bar, 50 nm). (b) Electron micrograph of a renal inner medullary collecting duct cell (scale bar, 100 nm). Uncoated vesicles (asterisks) and coated vesicles (arrow) are indicated. (c) Schematic of urinary exosome formation and release into the urine

References

1.            Ter-Ovanesyan, D., Exosomes: The Little Vesicles That Could, in Boston Biotech Watch. 2011, Boston Biotech Watch.

2.            Darwin, C., The Variation of Animals and Plants Under Domestication. 1868, London: John Murray.

3.            Pan, B.-T. and R.M. Johnstone, Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell, 1983. 33(3): p. 967-978.

4.            Thery, C., L. Zitvogel, and S. Amigorena, Exosomes; Composition, Biogenesis and Function. Nature Reviews, 2002. 1: p. 569-581.

5.            Johnstone, R.M., Revisiting the Road to the Discovery of Exosomes. Blood Cells, Molecules and Diseases, 2005. 34: p. 214-219.

6.            Johnstone, R.M., Exosomes Biological Significance: A Concise Review. Blood Cells, Molecules and Diseases, 2006. 36: p. 315-321.

7.            Alvarez-Erviti, L., et al., Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature biotechnology, 2011. 29(4): p. 341-345.