In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo: Part I: Health and Normal Physiology: Part I: Health and Normal Physiology

Abstract

Previously thought to be nothing more than cellular debris, extracellular vesicles (EVs) are now known to mediate physiological and pathological functions throughout the body. We now understand more about their capacity to transfer nucleic acids and proteins between distant organs, the interaction of their surface proteins with target cells, and the role of vesicle-bound lipids in health and disease. To date, most observations have been made in reductionist cell culture systems, or as snapshots from patient cohorts. The heterogenous population of vesicles produced in vivo likely act in concert to mediate both beneficial and detrimental effects. EVs play crucial roles in both the pathogenesis of diseases, from cancer to neurodegenerative disease, as well as in the maintenance of system and organ homeostasis. This two-part review draws on the expertise of researchers working in the field of EV biology and aims to cover the functional role of EVs in physiology and pathology. Part I will outline the role of EVs in normal physiology.

Keywords: exosomes; extracellular vesicles; in vivo; microvesicles; pathology; physiology.

FIGURE 1

EV signalling has been associated with every stage of reproduction: from sperm motility and protection, fertilisation, adhesion and implantation, and well as maternal‐foetal signalling in later pregnancy to protect the foetus from the mother's immune system. Taken from refs: (Al‐Dossary et al., ; Carlsson et al., ; Greening et al., ; Hedlund et al., ; Kauma et al., ; Knight et al., ; Miyado et al., ; Nguyen et al., ; Orozco et al., ; Palmerini et al., ; Pap et al., ; Park et al., ; Ronquist, ; Rooney et al., ; Salomon et al., ; Schuh et al., ; Stenqvist et al., ; Tong & Chamley, 2015)

FIGURE 2

Examples of EV‐mediated signalling within the CNS, and between the CNS and the periphery under healthy conditions. EVs have been shown to be released from all cells of the CNS: neurons (pink), microglia (yellow), astrocytes (purple), pericytes (orange) and endothelial cells (red), as well as oligodendrocytes. However, many of the EV‐mediated signalling pathways between these cells remain speculative. Given the difficulties in studying CNS‐derived EVs in vivo, there remain many key questions about communication between the various cell types. The information presented here summarises what we know about communication between these cells in vivo and is taken from refs: (Alvarez‐Erviti et al., ; Brown et al., ; Dickens et al., ; Lachenal et al., ; Mayo & Bearden, ; Morales‐Prieto et al., ; Obermeier et al., ; Paolicelli & Ferretti, ; Paolicelli et al., ; Sokolowski et al., ; Tanaka et al., ; Vyas et al., 2014)

FIGURE 3

Examples of EV signalling in homeostatic physiological processes. The majority of EV research is based on differences between diseases states and healthy controls, therefore knowledge of how EVs function in maintaining homeostasis is often unclear and understudied in vivo. This figure illustrates our knowledge of some of the key homeostatic processes in the body and the evidence we have of EVs playing a role in vivo. Taken from refs: (Choi et al., ; Cobelli et al., ; Coenen‐Stass et al., ; Davis et al., ; Deng et al., ; Forterre et al., ; Fry et al., ; Guescini et al., ; Huynh et al., ; Jalabert et al., ; Le Bihan et al., ; Li et al., ; Matsuzaka et al., ; Miyazawa et al., ; Oosthuyzen et al., ; Romancino et al., ; Street et al., ; Sun et al., ; Weilner et al., ; Whitham et al., 2018)