Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway
Abstract Objectives This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. Methods The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the t...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-09-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02087-8 |
| _version_ | 1827633260961726464 |
|---|---|
| author | PeiYao Zhang Panfeng Wu Umar Zeb Khan Zekun Zhou Xinlei Sui Cheng Li Kangkang Dong Yongjun Liu Liming Qing Juyu Tang |
| author_facet | PeiYao Zhang Panfeng Wu Umar Zeb Khan Zekun Zhou Xinlei Sui Cheng Li Kangkang Dong Yongjun Liu Liming Qing Juyu Tang |
| author_sort | PeiYao Zhang |
| collection | DOAJ |
| description | Abstract Objectives This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. Methods The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. Results LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1β signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. Conclusion LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival. |
| first_indexed | 2024-03-09T14:57:04Z |
| format | Article |
| id | doaj.art-5c8aebee5126473c820d9d4cc34805c9 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-09T14:57:04Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-5c8aebee5126473c820d9d4cc34805c92023-11-26T14:08:24ZengBMCJournal of Nanobiotechnology1477-31552023-09-0121111910.1186/s12951-023-02087-8Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathwayPeiYao Zhang0Panfeng Wu1Umar Zeb Khan2Zekun Zhou3Xinlei Sui4Cheng Li5Kangkang Dong6Yongjun Liu7Liming Qing8Juyu Tang9Department of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityDepartment of Orthopedics, Hand & Microsurgery Surgery, Xiangya Hospital of Central South UniversityAbstract Objectives This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. Methods The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. Results LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1β signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. Conclusion LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.https://doi.org/10.1186/s12951-023-02087-8Mesenchymal stromal cellsLPS preconditioningExosomeMacrophage polarizationAllograft |
| spellingShingle | PeiYao Zhang Panfeng Wu Umar Zeb Khan Zekun Zhou Xinlei Sui Cheng Li Kangkang Dong Yongjun Liu Liming Qing Juyu Tang Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway Journal of Nanobiotechnology Mesenchymal stromal cells LPS preconditioning Exosome Macrophage polarization Allograft |
| title | Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway |
| title_full | Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway |
| title_fullStr | Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway |
| title_full_unstemmed | Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway |
| title_short | Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway |
| title_sort | exosomes derived from lps preconditioned bone marrow derived msc modulate macrophage plasticity to promote allograft survival via the nf κb nlrp3 signaling pathway |
| topic | Mesenchymal stromal cells LPS preconditioning Exosome Macrophage polarization Allograft |
| url | https://doi.org/10.1186/s12951-023-02087-8 |
| work_keys_str_mv | AT peiyaozhang exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT panfengwu exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT umarzebkhan exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT zekunzhou exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT xinleisui exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT chengli exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT kangkangdong exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT yongjunliu exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT limingqing exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway AT juyutang exosomesderivedfromlpspreconditionedbonemarrowderivedmscmodulatemacrophageplasticitytopromoteallograftsurvivalviathenfkbnlrp3signalingpathway |