Improved detection of microparticles and exosomes is expected to provide an entirely new level of clinical information, which is likely to become an integral part of routine health care. 

In this month's Tune-In newsletter, we feature research on the study of these vesicles, by users of the qNano system at The University of Amsterdam and Harvard University.

Below: Researchers at AMC, University of Amsterdam with the qNano -- Edwin van der Pol (above), Marianne Schaap (below).

Microparticles and exosomes are microvesicles present in body fluids, derived from the plasma membrane of cells and platelets. They play important roles in normal processes (coagulation, inflammation, cellular homeostasis and survival, intercellular signaling, and transport of waste materials) as well as a number of disease states.

The size, concentration, and biochemical composition of these vesicles contain clinically relevant information – that is expected to lead to improved diagnosis and treatment of disease. However, because of the small size of most vesicles (30 nm – 1 µm), they are below the detection range of many currently used techniques.

Edwin van der Pol works with a team of researchers headed by Prof. Ton van Leeuwen and Dr. Rienk Nieuwland, at the Departments of Biomedical Engineering & Physics and the Laboratory for Experimental Clinical Chemistry, Academic Medical Center (AMC), University of Amsterdam.

The center is unique in that it evolved from a fusion of the Departments of Medical Physics and the Laser Center in 2008. With its expertise in haemodynamics, cardiovascular biophysics, and applications of biomedical photonics and quantitative medical imaging, the center regularly provides support for physicians and clinical researchers.

In preliminary experiments AMC researchers have shown that the qNano is capable of measuring the size and concentration of individual vesicles directly in suspension.

The group intend to combine the qNano with complimentary detection methods, so that parallel information on the biochemical composition of macromolecules inside living cells can be determined on a vesicle-by-vesicle basis.

“The simultaneous detection of the size, concentration, and biochemical composition from single vesicles would be a major step forward”, says van der Pol. “We expect that the improved detection of vesicles will provide an entirely new level of clinical information, which is likely to become an integral part of routine health care.”

Edwin will visit Izon’s Christchurch-based headquarters in August this year, to further work in this area.

For more information (requires Journal Access):
van der Pol E, Hoekstra AG, Sturk A, Otto C, van Leeuwen TG, Nieuwland R. Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost 2010; 8: 2596–607.

Dr. Jim Felton, Dr. Jeffrey Zwicker, Prof. Bruce Furie & Prof. Barbara Furie of Harvard University are conducting related work on microparticle analysis. Prof. Bruce Furie is Chief of the  Division of Hemostasis and Thrombosis at Harvard University’s Beth Israel Deaconess Medical Center, and Secretary General of the International Society of Thrombosis and Haemostasis (ISTH).

Of particular interest is how blood microparticles contribute towards the formation of blood clots or “thrombi”. An integral membrane protein known as tissue factor is recognized as having key importance in the initiation of a cascade of events, which result in thrombus formation.

It has long been held that thrombus formation is initiated primarily upon exposure of tissue factor present in extravascular tissue, such as the walls of blood vessels, after injury.

However, the Furie group have shown that the tissue-factor that contributes towards thrombus formation may be derived from other sources, including circulating microparticles.

Better understanding the role of tissue-factor bearing microparticles could reveal new information about thrombosis in vivo – which has implications for a number of conditions – such as cancer, sepsis, coronary heart disease and arterial bypass surgery.

Microparticles are widely implicated as playing a role in various pathological conditions, and could make potentially useful biomarkers for disease. Despite this, conventional analytical methods—such as flow cytometry, atomic force microscopy, dynamic light scattering, and coulter counting— have proven inadequate for accurate detection, identification and quantitation in plasma, which is a major obstacle to advancing research in this area.

For more information (requires Journal Access): Zwicker, J. et al. (2011) Tissue Factor-Bearing Microparticles and Thrombus Formation. Arterioscler Thromb Vasc Biol 2011;31;728-733; originally published online Jan 20.