Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria
Abstract Temporomandibular joint osteoarthritis (TMJOA) urgently needs regenerative therapies due to the limited effects of traditional treatments. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are considered a potent alternative for MSC therapy for the treatment of TMJOA. However,...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03478-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850231076891394048 |
|---|---|
| author | Ziyi Mei Hanyue Li Chuling Huang Shiyong Ma Yuejia Li Pingmeng Deng Sha Zhou Aizhuo Qian Bin Yang Jie Li |
| author_facet | Ziyi Mei Hanyue Li Chuling Huang Shiyong Ma Yuejia Li Pingmeng Deng Sha Zhou Aizhuo Qian Bin Yang Jie Li |
| author_sort | Ziyi Mei |
| collection | DOAJ |
| description | Abstract Temporomandibular joint osteoarthritis (TMJOA) urgently needs regenerative therapies due to the limited effects of traditional treatments. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are considered a potent alternative for MSC therapy for the treatment of TMJOA. However, the specific mechanisms remain inadequately investigated. In this study, we explored how EVs from adipose-derived stromal/stem cells (ASCs) influence the TMJOA model triggered by Complete Freund’s Adjuvant in rats and their impact on the state of dendritic cells (DCs) under pathological conditions. Subsequently, we conducted transcriptomic and metabolomic analyses to elucidate the specific mechanisms by which EVs affect DCs. Mechanistically, we demonstrate that EVs transferred functional mitochondria to DCs, which reverses their metabolic states. The internalized functional mitochondria from EVs activate the MAPK/ERK1/2/FoxO1/autophagy pathway, which causes the metabolic reprogramming of DCs and facilitates the achievement of therapeutic effects. These findings provide a mechanistic rationale for utilizing ASCs-EVs as cell-free alternatives to MSC transplantation in TMJOA therapy. Graphical Abstract |
| format | Article |
| id | doaj-art-582dbc7edfb24592bc8c7f3ce2faebe9 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-582dbc7edfb24592bc8c7f3ce2faebe92025-08-20T02:03:39ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123112010.1186/s12951-025-03478-9Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondriaZiyi Mei0Hanyue Li1Chuling Huang2Shiyong Ma3Yuejia Li4Pingmeng Deng5Sha Zhou6Aizhuo Qian7Bin Yang8Jie Li9College of Stomatology, Chongqing Medical UniversityDepartment of Stomatology, Shenzhen Hospital, Southern Medical UniversityCollege of Stomatology, Chongqing Medical UniversityBasic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, The Ministry of Education, College of Pharmacy, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityAbstract Temporomandibular joint osteoarthritis (TMJOA) urgently needs regenerative therapies due to the limited effects of traditional treatments. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are considered a potent alternative for MSC therapy for the treatment of TMJOA. However, the specific mechanisms remain inadequately investigated. In this study, we explored how EVs from adipose-derived stromal/stem cells (ASCs) influence the TMJOA model triggered by Complete Freund’s Adjuvant in rats and their impact on the state of dendritic cells (DCs) under pathological conditions. Subsequently, we conducted transcriptomic and metabolomic analyses to elucidate the specific mechanisms by which EVs affect DCs. Mechanistically, we demonstrate that EVs transferred functional mitochondria to DCs, which reverses their metabolic states. The internalized functional mitochondria from EVs activate the MAPK/ERK1/2/FoxO1/autophagy pathway, which causes the metabolic reprogramming of DCs and facilitates the achievement of therapeutic effects. These findings provide a mechanistic rationale for utilizing ASCs-EVs as cell-free alternatives to MSC transplantation in TMJOA therapy. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03478-9Extracellular vesiclesMitochondriaDendritic cellsAutophagyReprogramming metabolism |
| spellingShingle | Ziyi Mei Hanyue Li Chuling Huang Shiyong Ma Yuejia Li Pingmeng Deng Sha Zhou Aizhuo Qian Bin Yang Jie Li Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria Journal of Nanobiotechnology Extracellular vesicles Mitochondria Dendritic cells Autophagy Reprogramming metabolism |
| title | Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria |
| title_full | Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria |
| title_fullStr | Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria |
| title_full_unstemmed | Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria |
| title_short | Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria |
| title_sort | extracellular vesicles from adipose derived stromal stem cells reprogram dendritic cells to alleviate rat tmjoa by transferring mitochondria |
| topic | Extracellular vesicles Mitochondria Dendritic cells Autophagy Reprogramming metabolism |
| url | https://doi.org/10.1186/s12951-025-03478-9 |
| work_keys_str_mv | AT ziyimei extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT hanyueli extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT chulinghuang extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT shiyongma extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT yuejiali extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT pingmengdeng extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT shazhou extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT aizhuoqian extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT binyang extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria AT jieli extracellularvesiclesfromadiposederivedstromalstemcellsreprogramdendriticcellstoalleviaterattmjoabytransferringmitochondria |