Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction
Abstract Apoptosis is crucial for maintaining internal homeostasis. Apoptotic vesicles (ApoVs) derived from mesenchymal stem/ stromal cells (MSCs‐ApoVs) as natural lipid nanoparticles are attractive candidates for the next generation of immunotherapies. However, the therapeutic potential of MSCs‐Apo...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/advs.202407446 |
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| author | Anqi Liu Peng Peng Changze Wei Fanhui Meng Xiaoyao Huang Peisheng Liu Siyuan Fan Xinyue Cai Meiling Wu Zilin Xuan Qing Liu Xinyu Qiu Zhenlai Zhu Hao Guo |
| author_facet | Anqi Liu Peng Peng Changze Wei Fanhui Meng Xiaoyao Huang Peisheng Liu Siyuan Fan Xinyue Cai Meiling Wu Zilin Xuan Qing Liu Xinyu Qiu Zhenlai Zhu Hao Guo |
| author_sort | Anqi Liu |
| collection | DOAJ |
| description | Abstract Apoptosis is crucial for maintaining internal homeostasis. Apoptotic vesicles (ApoVs) derived from mesenchymal stem/ stromal cells (MSCs‐ApoVs) as natural lipid nanoparticles are attractive candidates for the next generation of immunotherapies. However, the therapeutic potential of MSCs‐ApoVs in managing hypersensitivity reactions mediated by CD8+ T cells remains elusive. This research utilized contact hypersensitivity and oral lichenoid reaction models, both of which represent type IV hypersensitivity reactions. ApoVs are shown that derived from stem cells from human exfoliated deciduous teeth (SHED‐ApoVs), a subtype of MSCs, directly fused with the plasma membrane of CD8+ T cells, subsequently increasing membrane permeability through L‐type voltage‐gated Ca2+ channels. This initiates a cascade of events including calcium overload, mitochondrial dysfunction, and the initiation of apoptosis in these cells. As known, this is the first study to characterize SHED‐ApoVs as immune microenvironment modulators, demonstrating their therapeutic potential and mechanism in these reactions. Moreover, analysis of blood samples from patients with oral lichenoid reactions verified the antihypersensitivity property of SHED‐ApoVs. This study sheds light on the therapeutic prospects of MSCs‐ApoVs and their underlying mechanisms in diseases mediated by CD8+ T cells, contributing novel perspectives for the clinical application of ApoVs and nanovesicle‐based cell‐free therapies. |
| format | Article |
| id | doaj-art-337b9bd9653840d7902c5f9be0ff3ec3 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-337b9bd9653840d7902c5f9be0ff3ec32025-08-20T03:44:51ZengWileyAdvanced Science2198-38442025-06-011222n/an/a10.1002/advs.202407446Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial DysfunctionAnqi Liu0Peng Peng1Changze Wei2Fanhui Meng3Xiaoyao Huang4Peisheng Liu5Siyuan Fan6Xinyue Cai7Meiling Wu8Zilin Xuan9Qing Liu10Xinyu Qiu11Zhenlai Zhu12Hao Guo13State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaDepartment of Chemical and Biomolecular Engineering National University of Singapore 4 Engineering Drive 4 Singapore 117585 SingaporeState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaFaculty of Medicine and Health University of Sydney Camperdown NSW 2050 AustraliaDepartment of Chemical and Biomolecular Engineering National University of Singapore 4 Engineering Drive 4 Singapore 117585 SingaporeState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Oral Medicine School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Disease Department of Preventive Dentistry School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 ChinaAbstract Apoptosis is crucial for maintaining internal homeostasis. Apoptotic vesicles (ApoVs) derived from mesenchymal stem/ stromal cells (MSCs‐ApoVs) as natural lipid nanoparticles are attractive candidates for the next generation of immunotherapies. However, the therapeutic potential of MSCs‐ApoVs in managing hypersensitivity reactions mediated by CD8+ T cells remains elusive. This research utilized contact hypersensitivity and oral lichenoid reaction models, both of which represent type IV hypersensitivity reactions. ApoVs are shown that derived from stem cells from human exfoliated deciduous teeth (SHED‐ApoVs), a subtype of MSCs, directly fused with the plasma membrane of CD8+ T cells, subsequently increasing membrane permeability through L‐type voltage‐gated Ca2+ channels. This initiates a cascade of events including calcium overload, mitochondrial dysfunction, and the initiation of apoptosis in these cells. As known, this is the first study to characterize SHED‐ApoVs as immune microenvironment modulators, demonstrating their therapeutic potential and mechanism in these reactions. Moreover, analysis of blood samples from patients with oral lichenoid reactions verified the antihypersensitivity property of SHED‐ApoVs. This study sheds light on the therapeutic prospects of MSCs‐ApoVs and their underlying mechanisms in diseases mediated by CD8+ T cells, contributing novel perspectives for the clinical application of ApoVs and nanovesicle‐based cell‐free therapies.https://doi.org/10.1002/advs.202407446apoptotic vesiclesCD8+ T cellsmesenchymal stem/stromal cellsmitochondrial dysfunctiontype IV hypersensitivity responses |
| spellingShingle | Anqi Liu Peng Peng Changze Wei Fanhui Meng Xiaoyao Huang Peisheng Liu Siyuan Fan Xinyue Cai Meiling Wu Zilin Xuan Qing Liu Xinyu Qiu Zhenlai Zhu Hao Guo Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction Advanced Science apoptotic vesicles CD8+ T cells mesenchymal stem/stromal cells mitochondrial dysfunction type IV hypersensitivity responses |
| title | Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction |
| title_full | Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction |
| title_fullStr | Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction |
| title_full_unstemmed | Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction |
| title_short | Apoptotic Vesicles Derived from Mesenchymal Stem Cells Ameliorate Hypersensitivity Responses via Inducing CD8+ T Cells Apoptosis with Calcium Overload and Mitochondrial Dysfunction |
| title_sort | apoptotic vesicles derived from mesenchymal stem cells ameliorate hypersensitivity responses via inducing cd8 t cells apoptosis with calcium overload and mitochondrial dysfunction |
| topic | apoptotic vesicles CD8+ T cells mesenchymal stem/stromal cells mitochondrial dysfunction type IV hypersensitivity responses |
| url | https://doi.org/10.1002/advs.202407446 |
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