Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms

Abstract Mesenchymal stem cells (MSCs), an accessible and less ethically controversial class of adult stem cells, have demonstrated significant efficacy in treating a wide range of diseases in both the preclinical and clinical phases. However, we do not yet have a clear understanding of the mechanis...

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Main Authors: Ruoxuan Wang, Jiao Fu, Jihui He, Xinxin Wang, Wenbo Xing, Xiaojing Liu, Juming Yao, Qingsong Ye, Yan He
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04211-x
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author Ruoxuan Wang
Jiao Fu
Jihui He
Xinxin Wang
Wenbo Xing
Xiaojing Liu
Juming Yao
Qingsong Ye
Yan He
author_facet Ruoxuan Wang
Jiao Fu
Jihui He
Xinxin Wang
Wenbo Xing
Xiaojing Liu
Juming Yao
Qingsong Ye
Yan He
author_sort Ruoxuan Wang
collection DOAJ
description Abstract Mesenchymal stem cells (MSCs), an accessible and less ethically controversial class of adult stem cells, have demonstrated significant efficacy in treating a wide range of diseases in both the preclinical and clinical phases. However, we do not yet have a clear understanding of the mechanisms by which MSCs exert their therapeutic effects in vivo. We found that the transplanted MSCs go an apoptotic fate within 24 h in vivo irrespective of the route of administration. Still, the short-term survival of MSCs do not affect their long-term therapeutic efficacy. An increasing number of studies have demonstrated that transplantation of apoptotic MSCs (ApoMSCs) show similar or even better efficacy than viable MSCs, including a variety of preclinical disease models such as inflammatory diseases, skin damage, bone damage, organ damage, etc. Although the exact mechanism has yet to be explored, recent studies have shown that transplanted MSCs undergo apoptosis in vivo and are phagocytosed by phagocytes, thereby exerting immunomodulatory effects. The apoptotic extracellular vesicles secreted by ApoMSCs (MSC-ApoEVs) play a significant role in promoting immunomodulation, endogenous stem cell regeneration, and angiogenesis due to their apoptotic properties and inheritance of molecular characteristics from their parental MSCs. On this basis, this review aims to deeply explore the therapeutic applications and mechanisms of ApoMSCs and their secretion of MSC-ApoEVs, as well as the challenges they face.
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spelling doaj-art-1a819ae0737249f8a3ee974fdf29b3eb2025-08-20T03:10:55ZengBMCStem Cell Research & Therapy1757-65122025-02-0116112610.1186/s13287-025-04211-xApoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanismsRuoxuan Wang0Jiao Fu1Jihui He2Xinxin Wang3Wenbo Xing4Xiaojing Liu5Juming Yao6Qingsong Ye7Yan He8Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyInstitute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyInstitute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyInstitute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyInstitute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyInstitute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyInstitute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyCenter of Regenerative Medicine, Renmin Hospital of Wuhan UniversityInstitute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and TechnologyAbstract Mesenchymal stem cells (MSCs), an accessible and less ethically controversial class of adult stem cells, have demonstrated significant efficacy in treating a wide range of diseases in both the preclinical and clinical phases. However, we do not yet have a clear understanding of the mechanisms by which MSCs exert their therapeutic effects in vivo. We found that the transplanted MSCs go an apoptotic fate within 24 h in vivo irrespective of the route of administration. Still, the short-term survival of MSCs do not affect their long-term therapeutic efficacy. An increasing number of studies have demonstrated that transplantation of apoptotic MSCs (ApoMSCs) show similar or even better efficacy than viable MSCs, including a variety of preclinical disease models such as inflammatory diseases, skin damage, bone damage, organ damage, etc. Although the exact mechanism has yet to be explored, recent studies have shown that transplanted MSCs undergo apoptosis in vivo and are phagocytosed by phagocytes, thereby exerting immunomodulatory effects. The apoptotic extracellular vesicles secreted by ApoMSCs (MSC-ApoEVs) play a significant role in promoting immunomodulation, endogenous stem cell regeneration, and angiogenesis due to their apoptotic properties and inheritance of molecular characteristics from their parental MSCs. On this basis, this review aims to deeply explore the therapeutic applications and mechanisms of ApoMSCs and their secretion of MSC-ApoEVs, as well as the challenges they face.https://doi.org/10.1186/s13287-025-04211-xMesenchymal stem cellsApoptotic extracellular vesiclesEfferocytosisAnti-inflammatoryCompensatory proliferation
spellingShingle Ruoxuan Wang
Jiao Fu
Jihui He
Xinxin Wang
Wenbo Xing
Xiaojing Liu
Juming Yao
Qingsong Ye
Yan He
Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms
Stem Cell Research & Therapy
Mesenchymal stem cells
Apoptotic extracellular vesicles
Efferocytosis
Anti-inflammatory
Compensatory proliferation
title Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms
title_full Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms
title_fullStr Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms
title_full_unstemmed Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms
title_short Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms
title_sort apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles therapeutic applications and mechanisms
topic Mesenchymal stem cells
Apoptotic extracellular vesicles
Efferocytosis
Anti-inflammatory
Compensatory proliferation
url https://doi.org/10.1186/s13287-025-04211-x
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