Therapeutically harnessing extracellular vesicles

The field of extracellular vesicle (EV) research has developed rapidly over the last decade from the study of fundamental biology to a subject of significant clinical relevance. The potential of harnessing EVs in the diagnosis and treatment of diseases — including cancer and neurological and cardiovascular disorders — is now being recognized. Accordingly, the applications of EVs as therapeutic targets, biomarkers, novel drug delivery agents and standalone therapeutics are being actively explored. Researchers from La Trobe University provide an overview of the characteristics and physiological functions of the various classes of EV, focusing on their association with disease and emerging strategies for their therapeutic exploitation.

The role of EVs in cancer, neurodegenerative diseases and cardiovascular disease

Extracellular vesicles (EVs) have roles in a range of diseases. Cancer-derived EVs contain various tumorigenic factors that have the ability to accelerate tumour growth and promote metastasis upon internalization into recipient healthy cells. They can also manipulate and prime supportive tissues in order to produce a microenvironment ideal for metastasis. Cancer-derived EVs can be used as diagnostic markers as they contain cargo that is representative of the parental cancerous cell. EVs can be released from neurons, astrocytes, oligodendrocytes and microglia under physiological conditions as a method of cell–cell communication. However, EVs containing neurotoxic proteins such as the infectious prion protein or amyloid-β (Aβ) can be involved in spreading pathological proteins to neighbouring healthy neurons, leading to neurodegenerative diseases such as prion disease and Alzheimer disease. Brain-derived EVs also contain proteins and microRNA (miRNA) that can break down the blood–brain barrier and potentially be released into the periphery, where they can be isolated in the blood and used as biomarkers for neurodegenerative diseases. EVs secreted from endothelial cells, smooth muscle cells, platelets and leukocytes can contain apoptotic factors and pro- and anti-inflammatory cytokines that contribute to the pathology of cardiovascular disease and cause atherosclerotic lesions and loss of myocardium function. The light blue boxes describe the ways in which EVs can be exploited therapeutically to target these diseases.