Research overview

Extracellular vesicles

Extracellular vesicles (EVs) are particles with a phospholipid bilayer that are released by cells into their environment. Consequently, body fluids, such as blood and urine, contain numerous EVs. Cells release EVs to communicate with other cells, to transport waste, and to fulfil functions to help the organism surviving, such as enhancing the coagulation of blood. To perform these functions, EVs contain genetic materials, lipids, proteins and sugars. This cargo can be used to reveal the type and state of the parent cell and therefore contains information about the health state of an organ. Thus, EVs in body fluids contain information that can help physicians making better medical decisions. In other words, EVs are biomarkers for diseases.

Challenges

EVs are claimed to “play a role” in virtually every biological process studied¹. On the other hand, only a few EV-based biomarkers have reached the clinic. There are five reasons EVs have thus far made limited impact to healthcare:

1. EVs are unstable after collection of the body fluid.
2. EVs are outnumbered by other particles with similar properties and functions.
3. Body fluids contain EVs from multiple cell types.
4. EVs are nanoparticles and therefore difficult to characterize.
5. Measurement results of EVs are difficult to interpret and compare due to a lack of standardization.

Research lines

Our research lines aim to address the challenges involved in functional characterization and biomarker development of EVs. We are working on improving pre-analytical procedures of EVs by stabilizing EVs and isolating EVs of interest from other EVs and particles. The evaluation of pre-analytical procedures requires reliable characterization of EVs. Therefore, we develop and improve measurement techniques, procedures and software to characterize EVs. We characterize the biochemical properties, such as antigen expression or mi-RNA content, the functional properties, such as the procoagulant activity, and the physical properties, such as dimension and concentration, of EVs.

Some measurement techniques require pure EV samples and hence there is a strong interaction between the research lines on pre-analytics and characterization of EVs. To publish reproducible data, we strive to standardize all aspects of our assays. Especially for the measurement techniques, standardization is challenging, because data are often measured in arbitrary units. To solve this issue, we collaborate with European metrology institutes and develop reference materials and procedures to express measurement results of EVs in standard units with known uncertainties. Standardization enables validation of the developed pre-analytical procedures and measurement techniques as well as reproduction of measurement results.

Being situated in the largest medical center of the Netherlands, we apply the developed standardized pre-analytical and analytical methods to search for EV-based biomarkers in clinical research studies.