Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis
Abstract Background Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of r...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02211-8 |
| _version_ | 1797556701268803584 |
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| author | Senrui Liu Shengwen Cheng Bowen Chen Pengcheng Xiao Jingdi Zhan Jiacheng Liu Zhuolin Chen Junyan Liu Tao Zhang Yiting Lei Wei Huang |
| author_facet | Senrui Liu Shengwen Cheng Bowen Chen Pengcheng Xiao Jingdi Zhan Jiacheng Liu Zhuolin Chen Junyan Liu Tao Zhang Yiting Lei Wei Huang |
| author_sort | Senrui Liu |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence. Result We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs. Conclusion The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA. |
| first_indexed | 2024-03-10T17:05:39Z |
| format | Article |
| id | doaj.art-243921da564b42d8bded9bb92f964ed7 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-10T17:05:39Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-243921da564b42d8bded9bb92f964ed72023-11-20T10:48:15ZengBMCJournal of Nanobiotechnology1477-31552023-11-0121111710.1186/s12951-023-02211-8Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritisSenrui Liu0Shengwen Cheng1Bowen Chen2Pengcheng Xiao3Jingdi Zhan4Jiacheng Liu5Zhuolin Chen6Junyan Liu7Tao Zhang8Yiting Lei9Wei Huang10Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Background Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence. Result We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs. Conclusion The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA.https://doi.org/10.1186/s12951-023-02211-8Cellular senescenceMitochondrial dysfunctionStem cellsResponsive hydrogelMicrovesicles |
| spellingShingle | Senrui Liu Shengwen Cheng Bowen Chen Pengcheng Xiao Jingdi Zhan Jiacheng Liu Zhuolin Chen Junyan Liu Tao Zhang Yiting Lei Wei Huang Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis Journal of Nanobiotechnology Cellular senescence Mitochondrial dysfunction Stem cells Responsive hydrogel Microvesicles |
| title | Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis |
| title_full | Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis |
| title_fullStr | Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis |
| title_full_unstemmed | Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis |
| title_short | Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis |
| title_sort | microvesicles hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis |
| topic | Cellular senescence Mitochondrial dysfunction Stem cells Responsive hydrogel Microvesicles |
| url | https://doi.org/10.1186/s12951-023-02211-8 |
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