Every second, our bodies depend on the proper functioning of trillions of cells, all working together to ensure we stay healthy – and to do so, they need to be able to communicate.
Cells send signals to each other via Extracellular Vesicles (EVs) – little packages of information which are then distributed to neighbouring cells. However, until now, their functions were not fully understood.
In this instalment of LIMS Explains, LIMS member and Director of the Research Centre for Extracellular Vesicles Professor Ivan Poon and recently graduated LIMS PhD student Jascinta Santavanond tell us what EVs are and the role they play and what they can tell us about disease. Professor Poon and Jascinta also outline how their recent research could help in the development of new diagnostic tools for patients with blood cancers, including leukaemia.
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What are Extracellular Vesicles (EVs), and what role do they play?
Extracellular Vesicles, or EVs, are small membrane packages of information which cells release as a way to communicate with neighbouring cells. Most types of cells in both plants and animals can produce EVs, they can vary in size, and the information they contain help cells work together.
Each EV contains information from the cell which released it, including proteins, carbohydrates, RNA and lipids. Once released, the EVs distribute these pieces of information to neighbouring cells - a bit like a delivery truck dropping off parcels. The information fragments then either attach to, or are engulfed by, destination cells.
What can EVs tell us about disease?
The origin, amount, and size of EVs, as well as what they contain, can give us an idea of what could be happening to the cell. For example, certain levels of RNA molecules, lipids or proteins, or even just very large EVs could be indicative of a cell which is in a disease state or under stress.
EV behaviour in cancer is also an interesting example. In certain types of cancer, the cancerous cells can manipulate their environment by releasing very large EVs containing tumour DNA and other elements which help the cancer spread to other cells, allowing tumours to grow and thrive.
EV production caused by tissue damage is an area which is currently of great interest. Recently, we contributed to research with colleagues at the Walter and Eliza Hall Institute of Medical Research (WEHI) which examined the production and behaviour of EVs from endothelial cells – the type of cells which line blood vessels – in zebrafish, mice and humans.
Published in Nature Communications, we found that when the endothelial cells are dying or under stress, they produce large EVs full of cellular waste – in this case, lots of damaged mitochondria, the chemical powerhouses which help the cells function properly
These larger EVs also include the lipid phosphatidylserine, which functions as an “eat me” marker – a signal for nearby immune cells to clear the EVs away for recycling.
Your recent research developed a new technique to see how EVs behave in real time. What was the research and how did you do it?
Historically, there have been many different reasons why EVs were tricky to study. Firstly, because they’re so tiny, microscopy technology needed to be developed to be able to see not just the EVs themselves but also what they contain.
Another challenge was that even when that technology was developed, EVs are often examined from samples collected from a tissue or in a culture dish. Although you can identify EVs in a sample, it is hard to understand why they are produced, or even if they form within an organism at all.
For this research, the LIMS research team utilised a microscopy technique to investigate endothelial cell EV production in mice and also living zebrafish, which are transparent in their early stages of development. This gave us a unique opportunity to monitor the development of the vascular system and formation of EVs in these blood vessels in real time.
We used the technique to investigate healthy endothelial cells as well as those affected by leukaemia, and found not only that EVs are indeed produced within the organism but also that when the endothelial cells were under stress or dying because of the cancer, they sent out the large, waste-laden EVs for clearance by immune cells.
How could understanding EVs better help patients in the future?
Having a better understanding of the role EVs play in the body could give scientists new avenues of research to pursue to better understand the effects of disease and how the body responds to it, as well as creating opportunities for the development of new, better treatments.
We hope our research opens the way for the development of new diagnostic tools which measure large endothelial cell EV levels to indicate the amount of tissue damage observed during disease, including blood cancers such as leukaemia. This could help clinicians better diagnose and care for patients by giving them the ability to more easily assess the extent of vascular tissue damage.
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Professor Ivan Poon and Jasinta Santavanond recently contributed to the research paper, “In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions”. The study was led by LIMS Alumna and WEHI researcher Dr Georgia Atkin-Smith, Professor Poon and WEHI’s Associate Professor Edwin Hawkins, with recently graduated LIMS PhD student Jascinta Santavanond contributing as the paper’s second author.
Read the paper here at Nature Communications.
