Apoptotic vesicles: emerging concepts and research progress in physiology and therapy

Apoptosis represents the dominant form of programmed cell death and plays critical roles in maintaining tissue and organ homeostasis. A notable population of extracellular vesicles (EVs) is generated during apoptosis, known as apoptotic vesicles (apoVs). These apoVs are increasingly the subject of studies concerning their identity and mechanisms of production, which have been revealed unique biological and functional characteristics that are emerging as crucial regulators for diverse processes. Furthermore, apoVs have been gradually noticed for their essential role in regulating the physiology of various organ systems in vivo, and growing evidence suggests that apoV dysregulation contributes to age- and pathology-associated tissue alterations. Importantly, apoVs can be therapeutically harnessed to unleash their potential in treating several diseases such as immune disorders, osteoporosis, cutaneous wound and acute liver failure; these vesicles, mainly derived from cultured mesenchymal stem cells, hold great translational promise. Here we review the current landscape of scientific knowledge about apoVs, with emphasis on mechanistic insights into how apoVs contribute to organismal health and disease, which also provide novel cell-free strategies for EV-based regenerative therapeutics.