Exploring the frontiers of EVs & exosomes research

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By David McFadden

Research Writer & Communications Advisor, Faculty of Medicine

Our broad research community has emerged as a true innovator in EV/exosomes research, making new discoveries with potentially broad impact.

Medical research into extracellular vesicles (EVs) and exosomes has been a rapidly evolving area of multidisciplinary exploration.  Once dismissed as cellular trash, these nanometer-scale particles have increasingly become a hot topic in everything from biological cancer therapy and targeted drug investigation to early disease detection.

What are they? Imagine tiny, information-laden bubbles naturally secreted by cells. They are packed with bioactive proteins, lipids, and genetic material. Because they can carry and deliver a remarkable range of miniscule cargo, they play an essential role as intercellular messengers in both physiology and pathology.

Not only do they hold promise as biomarkers – levels of proteins or other substances that can signify disease – but they can also carry RNA and other active substances between cells, giving them advantages for drug delivery. They play roles in maintaining tissue homeostasis and regulating metabolism and immune responses. And, strikingly, some EVs display the ability to cross the blood–brain barrier, meaning they can travel into the brain when in the blood stream.

“In recent years, our broad research community – made up of the uOttawa Faculty of Medicine and affiliated institutes and hospitals including The Ottawa Hospital (TOH)  and CHEO– has emerged as a true innovator in EV/exosomes research, making new discoveries with potentially broad impact. Multiple researchers are doing globally competitive work that is enabling scientists to better understand the potential of these ultra-tiny structures,” says Dr. Jocelyn Côté, Vice-Dean for Research and a full professor in the Department of Cellular and Molecular Medicine.

Cells and exosomes
A rendition of cells secreting extracellular vesicles (EVs).

To name just a few teams that have earned widespread attention: Dr. Derrick Gibbings’ leading efforts to unveil EV-mediated RNA communication, Dr. Bernard Thébaud’s efforts to utilize stem cells and EVs as a therapy for lung injury, and the work of Dr. John Bell and Dr. Carolina Ilkow to use EVs and a novel viral technology to advance immunotherapy, a type of cancer treatment.

While there’s no shortage of groups across the globe that are investigating EVs and exosomes, members of our thriving collaborative ecosystem are approaching problems from unique angles and developing world-first findings.

“We’re solving problems that others didn’t manage to solve. For example, figuring out how EVs can work as effective delivery vehicles,” says Dr. Gibbings, whose uOttawa lab discovered a mechanism that traffics RNA and microRNA complexes into exosomes and, with a drug company, turned their discovery into a diagnostic test that’s now used in the clinic.

Dr. Derrick Gibbings

Ultimately, Dr. Gibbings’ long-term goal is to understand how exosomes package and traffic RNA throughout the body and apply this to revolutionize drug delivery by using exosomes to deliver large drugs, including doubled-stranded RNA known as “small interfering RNA” (siRNA).

Dr. Dylan Burger, whose lab was the first to use flow cytometry to assess urinary extracellular vesicles and the first to show that increases in levels of these vesicles in urine may be an early sign of diabetic kidney disease, says our research community is increasingly prominent in this international research space.

“There is definitely great enthusiasm for the work coming out of the uOttawa/TOH,” says Dr. Burger, who is co-chair of the Urine Task Force of the International Society of Extracellular Vesicles.

Investigators’ EVs and exosomes research is massively aided by the Faculty of Medicine’s Flow Cytometry & Virometry (FCV) Core Facility, which is internationally recognized for its excellence in small particle (EVs and virus) analysis. The considerable expertise of facility manager Dr. Vera Tang has given our research community a big leg-up with advanced flow cytometry.

Vera Tang
Dr. Vera Tang, manager of the Faculty of Medicine’s Flow Cytometry & Virometry (FCV) Core Facility.

Dr. Tang routinely engages with the global EVs and flow cytometry community. For instance, she’s part of an international working group for EV flow cytometry and is regularly tapped for training other laboratories in the latest approaches.

Dr. Tang says the core facility utilizes a method of quantitative flow cytometry that involves optimization and calibration of instruments. Two cutting-edge instruments in the core’s fleet – the Cytek Aurora ESP and CytoFLEX S flow cytometers – have a lower limit of about 100nm to help detect ultra-tiny biological particles such as EVs and viruses.

“We contribute our expertise to help scientists better utilize the scientific instruments so that they can focus on understanding the biology,” Dr. Tang says.

In Dr. Burger’s view: “To put it simply, the fact that I conduct my EV analysis through the uOttawa flow cytometry core gives me instant credibility amongst the international community.”

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