Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis
Abstract The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we rep...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41529-7 |
| _version_ | 1827710173602381824 |
|---|---|
| author | Ting Huang Ruyi Lin Yuanqin Su Hao Sun Xixi Zheng Jinsong Zhang Xiaoyan Lu Baiqin Zhao Xinchi Jiang Lingling Huang Ni Li Jing Shi Xiaohui Fan Donghang Xu Tianyuan Zhang Jianqing Gao |
| author_facet | Ting Huang Ruyi Lin Yuanqin Su Hao Sun Xixi Zheng Jinsong Zhang Xiaoyan Lu Baiqin Zhao Xinchi Jiang Lingling Huang Ni Li Jing Shi Xiaohui Fan Donghang Xu Tianyuan Zhang Jianqing Gao |
| author_sort | Ting Huang |
| collection | DOAJ |
| description | Abstract The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we report the generation of high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated mitochondrial transfer to injured lung cells by the sequential treatment of pioglitazone and iron oxide nanoparticles. This highly efficient mitochondrial transfer is shown to not only restore mitochondrial homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse to show that these high-powered mesenchymal stem cells successfully mitigate fibrotic progression in a progressive fibrosis model, which was further verified in a humanized multicellular lung spheroid model. The present findings provide a potential strategy to overcome the current limitations in mitochondrial replenishment therapy, thereby promoting therapeutic applications for fibrotic intervention. |
| first_indexed | 2024-03-10T17:33:28Z |
| format | Article |
| id | doaj.art-423879c2cadb442f91cd65e219d67582 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:33:28Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-423879c2cadb442f91cd65e219d675822023-11-20T09:55:16ZengNature PortfolioNature Communications2041-17232023-09-0114111510.1038/s41467-023-41529-7Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesisTing Huang0Ruyi Lin1Yuanqin Su2Hao Sun3Xixi Zheng4Jinsong Zhang5Xiaoyan Lu6Baiqin Zhao7Xinchi Jiang8Lingling Huang9Ni Li10Jing Shi11Xiaohui Fan12Donghang Xu13Tianyuan Zhang14Jianqing Gao15College of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang UniversityDepartment of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of MedicineCollege of Pharmaceutical Sciences, Zhejiang UniversityDepartment of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Cardiothoracic Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo UniversitySchool of Pharmaceutical Sciences, Hangzhou Medical CollegeCollege of Pharmaceutical Sciences, Zhejiang UniversityDepartment of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of MedicineCollege of Pharmaceutical Sciences, Zhejiang UniversityCollege of Pharmaceutical Sciences, Zhejiang UniversityAbstract The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we report the generation of high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated mitochondrial transfer to injured lung cells by the sequential treatment of pioglitazone and iron oxide nanoparticles. This highly efficient mitochondrial transfer is shown to not only restore mitochondrial homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse to show that these high-powered mesenchymal stem cells successfully mitigate fibrotic progression in a progressive fibrosis model, which was further verified in a humanized multicellular lung spheroid model. The present findings provide a potential strategy to overcome the current limitations in mitochondrial replenishment therapy, thereby promoting therapeutic applications for fibrotic intervention.https://doi.org/10.1038/s41467-023-41529-7 |
| spellingShingle | Ting Huang Ruyi Lin Yuanqin Su Hao Sun Xixi Zheng Jinsong Zhang Xiaoyan Lu Baiqin Zhao Xinchi Jiang Lingling Huang Ni Li Jing Shi Xiaohui Fan Donghang Xu Tianyuan Zhang Jianqing Gao Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis Nature Communications |
| title | Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis |
| title_full | Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis |
| title_fullStr | Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis |
| title_full_unstemmed | Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis |
| title_short | Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis |
| title_sort | efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis |
| url | https://doi.org/10.1038/s41467-023-41529-7 |
| work_keys_str_mv | AT tinghuang efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT ruyilin efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT yuanqinsu efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT haosun efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT xixizheng efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT jinsongzhang efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT xiaoyanlu efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT baiqinzhao efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT xinchijiang efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT linglinghuang efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT nili efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT jingshi efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT xiaohuifan efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT donghangxu efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT tianyuanzhang efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis AT jianqinggao efficientinterventionforpulmonaryfibrosisviamitochondrialtransferpromotedbymitochondrialbiogenesis |