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Dr Yuliya Shakalisava, who led the EU-funded METAFORA project at Leiden University in the Netherlands, has laid the foundations for an entirely novel approach to diagnosing disease using exosomes, nanoscale ‘bubbles’ released by all types of cells. When the technology is ready, she says, it has the potential to provide answers to previously unanswered questions about disease mechanisms.
Once thought to be waste products of cellular processes, extracellular vesicles are now known to be important messengers, carrying information from one cell to another. Significantly, they are found in all bodily fluids, from blood and urine to tears – enabling samples to be obtained from hard-to-reach organs such as the brain, heart and liver without the patient having to undergo invasive medical procedures.
‘The approach to isolating extracellular vesicles from body fluids developed in this project was completely novel for this area of research. It should help to identify potential biomarkers to diagnose disease and develop new therapeutic strategies. However, isolating and separating exosomes from bodily fluids is very challenging. METAFORA proposed a new way to solve this problem,’ Shakalisava explains.
Innovative microfluidics
To separate exosomes from biological fluids, Shakalisava made use of their electrophoretic mobility – i.e. how fast they move in the electric field in a micrometre-sized channel, a physical property that is unique to each molecule or particle.
The microfluidic technology could potentially allow exosomes to be extracted from fluid samples and analysed in just minutes, instead of the hours or days of laboratory work currently required.
That, in turn, could eventually enable the development of a novel range of diagnostic tools allowing doctors to look for biomarkers of different diseases quickly and efficiently in a clinical setting.
‘We took an important step toward finding the solution. It could be a novel way of performing a liquid biopsy – a non-invasive way to obtain molecular information about the cells and organs from bodily liquids such as blood and urine. This could lead to early diagnosis of disease and timely monitoring of treatment,’ Shakalisava says.
Insights into disease mechanisms
For example, a key focus of Shakalisava’s research was how exosomes could provide new insights into the mechanisms underlying microvascular disease which affects small blood vessels triggered by continuous exposure to high blood pressure and diabetes. The disease causes the loss of capillaries, leading to heart and kidney failure and other terminal conditions.
‘There is still no effective treatment and the mechanism of this disease is not fully understood. For example, we still don’t know why some diabetic patients are affected by the loss of tissue capillaries but others are not,’ she says.
The techniques developed in METAFORA, with the support of the EU’s Marie Skłodowska-Curie Actions programme, could shed light on that question, while also helping to diagnose and understand many other conditions. An educational booklet, Catch the Exosomes, produced by Shakalisava and artist Annett von Katz, explains the technology and its potential.
Shakalisava is currently further developing the approach to explore Alzheimer’s disease in a follow-up project, an ERA-NET cofund in nanomedicine called EXIT.
‘METAFORA was a stepping stone to a larger-scale collaborative project to use the microfluidic technology concept for the analysis of exosomes in the investigation of Alzheimer’s disease. The aim of this project is to raise the technology readiness level towards a commercial product,’ she concludes.