Extracellular Vesicles Arising from Apoptosis: Forms, Functions and Applications

Extracellular vesicles (EVs) are lipid bilayer-enclosed subcellular bodies produced by most, if not all cells. Research, especially over the last two decades, has recognised the importance of EVs in intercellular communication and horizontal transfer of biological material. EVs range in diameter from tens of nanometres up to several micrometres and are able to transfer a spectrum of biologically active cargoes – from whole organelles, through macromolecules including nucleic acids and proteins, to metabolites and small molecules – from their cells of origin to recipient cells, which may consequently become physiologically or pathologically altered. Based on their modes of biogenesis, the most renowned EV classes are (1) microvesicles (MVs), (2) exosomes (both produced by healthy cells), and (3) EVs from cells undergoing regulated death by apoptosis (ApoEVs). MVs bud directly from the plasma membrane, while exosomes are derived from endosomal compartments. Current knowledge of the formation and functional properties of ApoEVs lags behind that of MVs and exosomes but burgeoning evidence indicates that ApoEVs carry manifold cargoes including mitochondria, ribosomes, DNA, RNAs and proteins, and perform diverse functions in health and disease. Here we review this evidence, which demonstrates substantial diversity in the luminal and surface membrane cargoes of ApoEVs, permitted by their very broad size range (from around 50 nanometres to >5 micrometres; the larger often termed apoptotic bodies), strongly suggests their origins through both MV- and exosome-like biogenesis pathways and indicates routes through which they interact with recipient cells. We discuss the capacity of ApoEVs to recycle cargoes, to modulate inflammatory, immunological and cell fate programmes in normal physiology and in pathological scenarios such as cancer and atherosclerosis. Finally, we provide a perspective on clinical applications of ApoEVs in diagnostics and therapeutics.