Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles
Abstract Background Bone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is f...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-01-01
|
| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-023-00422-3 |
| _version_ | 1811171634589990912 |
|---|---|
| author | Xueke Li Yi Zhong Wuqi Zhou Yishu Song Wenqu Li Qiaofeng Jin Tang Gao Li Zhang Mingxing Xie |
| author_facet | Xueke Li Yi Zhong Wuqi Zhou Yishu Song Wenqu Li Qiaofeng Jin Tang Gao Li Zhang Mingxing Xie |
| author_sort | Xueke Li |
| collection | DOAJ |
| description | Abstract Background Bone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell–cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects. Methods BMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation. Results In this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs. Conclusion LIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects. |
| first_indexed | 2024-04-10T17:17:21Z |
| format | Article |
| id | doaj.art-88266eff86a746be960f6ccf274e8621 |
| institution | Directory Open Access Journal |
| issn | 1689-1392 |
| language | English |
| last_indexed | 2024-04-10T17:17:21Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-88266eff86a746be960f6ccf274e86212023-02-05T12:18:39ZengBMCCellular & Molecular Biology Letters1689-13922023-01-0128112110.1186/s11658-023-00422-3Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesiclesXueke Li0Yi Zhong1Wuqi Zhou2Yishu Song3Wenqu Li4Qiaofeng Jin5Tang Gao6Li Zhang7Mingxing Xie8Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Bone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell–cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects. Methods BMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation. Results In this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs. Conclusion LIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects.https://doi.org/10.1186/s11658-023-00422-3Low-intensity pulsed ultrasoundExtracellular vesiclesInflammationBone marrow mesenchymal stem cellsmicroRNA |
| spellingShingle | Xueke Li Yi Zhong Wuqi Zhou Yishu Song Wenqu Li Qiaofeng Jin Tang Gao Li Zhang Mingxing Xie Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles Cellular & Molecular Biology Letters Low-intensity pulsed ultrasound Extracellular vesicles Inflammation Bone marrow mesenchymal stem cells microRNA |
| title | Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles |
| title_full | Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles |
| title_fullStr | Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles |
| title_full_unstemmed | Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles |
| title_short | Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles |
| title_sort | low intensity pulsed ultrasound lipus enhances the anti inflammatory effects of bone marrow mesenchymal stem cells bmscs derived extracellular vesicles |
| topic | Low-intensity pulsed ultrasound Extracellular vesicles Inflammation Bone marrow mesenchymal stem cells microRNA |
| url | https://doi.org/10.1186/s11658-023-00422-3 |
| work_keys_str_mv | AT xuekeli lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT yizhong lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT wuqizhou lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT yishusong lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT wenquli lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT qiaofengjin lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT tanggao lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT lizhang lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles AT mingxingxie lowintensitypulsedultrasoundlipusenhancestheantiinflammatoryeffectsofbonemarrowmesenchymalstemcellsbmscsderivedextracellularvesicles |