The role of mesenchymal stem cell-derived extracellular vesicles in inflammation-associated programmed cell death

Mesenchymal stem cells (MSCs), as a kind of pluripotent adult stem cell capable of exhibiting immunomodulatory properties, have been extensively studied in basic scientific research and clinical applications in inflammatory diseases. MSC-derived extracellular vesicles (MSC-EVs) are receiving increasingly attention as a major pathway for MSCs to exert intercellular communication. It has been demonstrated that programmed cell death (PCD) plays a critical role in the pathophysiology of human diseases, mainly including apoptosis, necroptosis, pyroptosis, fer-roptosis, autophagy-dependent cell death, and other modalities. Recent studies have documented that MSCs are capable of regulating other types of PCD in addition to their antiapoptotic effects. Here, we review the potential influences of MSC-EVs on different types of PCD and diseases, categorize the differences in the therapeutic effects of MSC-EVs from various sources and interventional measures, compile the current research progress of PCD-related elements in clinical trials of MSC-EVs, and finally present the advantages and challenges of clinical ap-plications of MSC-EVs. This review summarizes the updated advances in the regulation of inflammation-asso-ciated PCD by MSC-EVs, which are important for gaining insight into the molecular mechanisms and modulatory targets for inflammation-associated PCD. (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).