Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5p
Background. Sepsis-induced acute lung injury is a common critical illness in intensive care units with no effective treatment is currently available. Small extracellular vesicles, secreted by mesenchymal stem cells (MSCs), derived from human-induced pluripotent stem cells (iMSC-sEV), possess strikin...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2023/8987049 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832546558969643008 |
|---|---|
| author | Wei Peng Yun Yang Jiaquan Chen Zeyao Xu Yuanlei Lou Qi Li Ning Zhao Kejian Qian Fen Liu |
| author_facet | Wei Peng Yun Yang Jiaquan Chen Zeyao Xu Yuanlei Lou Qi Li Ning Zhao Kejian Qian Fen Liu |
| author_sort | Wei Peng |
| collection | DOAJ |
| description | Background. Sepsis-induced acute lung injury is a common critical illness in intensive care units with no effective treatment is currently available. Small extracellular vesicles, secreted by mesenchymal stem cells (MSCs), derived from human-induced pluripotent stem cells (iMSC-sEV), possess striking advantages when incorporated MSCs and iPSCs, which are considered extremely promising cell-free therapeutic agents. However, no studies have yet been conducted to systemically examine the effects and underlying mechanisms of iMSC-sEV application on attenuated lung injury under sepsis conditions. Method. iMSC-sEV were intraperitoneally administered in a rat septic lung injury model induced by cecal ligation and puncture (CLP). The efficacy of iMSC-sEV was assessed by histology, immunohistochemistry, and pro-inflammatory cytokines of bronchoalveolar lavage fluid. We also evaluated the in vitro effects of iMSC-sEV on the activation of the inflammatory response in alveolar macrophages (AMs). Small RNA sequencing was utilized to detect changes in the miRNA expression profile in lipopolysaccharide (LPS)-treated AMs after iMSC-sEV administration. The effects of miR-125b-5p on the function of AMs were studied. Results. iMSC-sEV were able to attenuate pulmonary inflammation and lung injury following CLP-induced lung injury. iMSC-sEV were internalized by AMs and alleviated the release of inflammatory factors by inactivating the NF-κB signaling pathway. Moreover, miR-125b-5p showed a fold-change in LPS-treated AMs after iMSC-sEV administration and was enriched in iMSC-sEV. Mechanistically, iMSC-sEV transmitted miR-125b-5p into LPS-treated AMs to target TRAF6. Conclusion. Our findings demonstrated that iMSC-sEV treatment protects against septic lung injury and exerts anti-inflammatory effects on AMs at least partially through miR-125b-5p, suggesting that iMSC-sEV may provide a novel cell-free strategy for the treatment of septic lung injury. |
| format | Article |
| id | doaj-art-d0eb73e89bb04f3a9cbd7573106ef12e |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-d0eb73e89bb04f3a9cbd7573106ef12e2025-02-03T06:48:31ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/8987049Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5pWei Peng0Yun Yang1Jiaquan Chen2Zeyao Xu3Yuanlei Lou4Qi Li5Ning Zhao6Kejian Qian7Fen Liu8Department of Critical Care MedicineDepartment of Critical Care MedicineDepartment of Critical Care MedicineDepartment of Critical Care MedicineInstitute of UrologyDepartment of Critical Care MedicineDepartment of Critical Care MedicineDepartment of Critical Care MedicineDepartment of Critical Care MedicineBackground. Sepsis-induced acute lung injury is a common critical illness in intensive care units with no effective treatment is currently available. Small extracellular vesicles, secreted by mesenchymal stem cells (MSCs), derived from human-induced pluripotent stem cells (iMSC-sEV), possess striking advantages when incorporated MSCs and iPSCs, which are considered extremely promising cell-free therapeutic agents. However, no studies have yet been conducted to systemically examine the effects and underlying mechanisms of iMSC-sEV application on attenuated lung injury under sepsis conditions. Method. iMSC-sEV were intraperitoneally administered in a rat septic lung injury model induced by cecal ligation and puncture (CLP). The efficacy of iMSC-sEV was assessed by histology, immunohistochemistry, and pro-inflammatory cytokines of bronchoalveolar lavage fluid. We also evaluated the in vitro effects of iMSC-sEV on the activation of the inflammatory response in alveolar macrophages (AMs). Small RNA sequencing was utilized to detect changes in the miRNA expression profile in lipopolysaccharide (LPS)-treated AMs after iMSC-sEV administration. The effects of miR-125b-5p on the function of AMs were studied. Results. iMSC-sEV were able to attenuate pulmonary inflammation and lung injury following CLP-induced lung injury. iMSC-sEV were internalized by AMs and alleviated the release of inflammatory factors by inactivating the NF-κB signaling pathway. Moreover, miR-125b-5p showed a fold-change in LPS-treated AMs after iMSC-sEV administration and was enriched in iMSC-sEV. Mechanistically, iMSC-sEV transmitted miR-125b-5p into LPS-treated AMs to target TRAF6. Conclusion. Our findings demonstrated that iMSC-sEV treatment protects against septic lung injury and exerts anti-inflammatory effects on AMs at least partially through miR-125b-5p, suggesting that iMSC-sEV may provide a novel cell-free strategy for the treatment of septic lung injury.http://dx.doi.org/10.1155/2023/8987049 |
| spellingShingle | Wei Peng Yun Yang Jiaquan Chen Zeyao Xu Yuanlei Lou Qi Li Ning Zhao Kejian Qian Fen Liu Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5p Journal of Immunology Research |
| title | Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5p |
| title_full | Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5p |
| title_fullStr | Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5p |
| title_full_unstemmed | Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5p |
| title_short | Small Extracellular Vesicles Secreted by iPSC-Derived MSCs Ameliorate Pulmonary Inflammation and Lung Injury Induced by Sepsis through Delivery of miR-125b-5p |
| title_sort | small extracellular vesicles secreted by ipsc derived mscs ameliorate pulmonary inflammation and lung injury induced by sepsis through delivery of mir 125b 5p |
| url | http://dx.doi.org/10.1155/2023/8987049 |
| work_keys_str_mv | AT weipeng smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT yunyang smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT jiaquanchen smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT zeyaoxu smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT yuanleilou smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT qili smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT ningzhao smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT kejianqian smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p AT fenliu smallextracellularvesiclessecretedbyipscderivedmscsamelioratepulmonaryinflammationandlunginjuryinducedbysepsisthroughdeliveryofmir125b5p |