Extracellular vesicles arising from apoptosis: forms, functions, and applications

Abstract

Extracellular vesicles (EVs) are lipid bilayer‐enclosed subcellular bodies produced by most, if not all cells. Research 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, (2) exosomes (both produced by healthy cells), and (3) EVs from cells undergoing regulated death by apoptosis (ApoEVs). Microvesicles 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 microvesicles 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 nm to >5 μm; the larger often termed apoptotic bodies), strongly suggests their origins through both microvesicle‐ and exosome‐like biogenesis pathways, and indicates routes through which they interact with recipient cells. We discuss the capacity of ApoEVs to recycle cargoes and 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. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Hijacking homeostasis: Regulation of the tumor microenvironment by apoptosis

“…Further aspects of cargo loading of ApoBDs and other ApoEVs have been reviewed recently. 125 , 129 , 151 …”

“…Recent appraisals of the functional properties of ApoBDs, which include immunomodulation, coagulation and AiP have been provided recently. 125 , 129 , 151 …”

“… 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 A recent detailed review of the molecular cell biology of ApoEVs is also available. 151 Although it is well appreciated that EV production is generally increased as a consequence of apoptosis, knowledge of the biological and clinical aspects of ApoEVs lags behind the EV field in general which has been largely focused on EVs derived from healthy cells.…”

Recent Advances in Pathology: the 2023 Annual Review Issue of The Journal of Pathology

“…Moreover, the ever‐expanding datasets, increased computational power, and the potential for integration of experimental data mean there is exciting potential for the future. The next article, from Gregory and Rimmer in Edinburgh, Scotland, reviews the recent progress in understanding the properties and effects of extracellular vesicles (EVs), involved in intercellular communication and the horizontal transfer of cellular components [7]. EVs are produced by most cells, if not all, with healthy cells producing microvesicles and exosomes, whilst EVs are also produced from cells undergoing regulated death by apoptosis (termed ApoEVs).…”

Functional diversity of apoptotic vesicle subpopulations from bone marrow mesenchymal stem cells in tissue regeneration

“…Apoptosis, the orchestrated mechanism of cellular self‐demise, transcends its role as the foundation of life maintenance and development in multicellular organisms (Gregory & Rimmer, 2023 ; Lockshin & Zakeri, 2007 ; Zhang et al., 2023 ; Zhu et al., 2023 ). Distinguished from cellular necrosis, apoptosis unfolds as a highly orchestrated and meticulously controlled cascade of self‐destruction.…”