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Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis

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...

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Autores principales: Liu, Senrui, Cheng, Shengwen, Chen, Bowen, Xiao, Pengcheng, Zhan, Jingdi, Liu, Jiacheng, Chen, Zhuolin, Liu, Junyan, Zhang, Tao, Lei, Yiting, Huang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652587/
https://www.ncbi.nlm.nih.gov/pubmed/37968657
http://dx.doi.org/10.1186/s12951-023-02211-8
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author Liu, Senrui
Cheng, Shengwen
Chen, Bowen
Xiao, Pengcheng
Zhan, Jingdi
Liu, Jiacheng
Chen, Zhuolin
Liu, Junyan
Zhang, Tao
Lei, Yiting
Huang, Wei
author_facet Liu, Senrui
Cheng, Shengwen
Chen, Bowen
Xiao, Pengcheng
Zhan, Jingdi
Liu, Jiacheng
Chen, Zhuolin
Liu, Junyan
Zhang, Tao
Lei, Yiting
Huang, Wei
author_sort Liu, Senrui
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02211-8.
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spelling pubmed-106525872023-11-15 Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis Liu, Senrui Cheng, Shengwen Chen, Bowen Xiao, Pengcheng Zhan, Jingdi Liu, Jiacheng Chen, Zhuolin Liu, Junyan Zhang, Tao Lei, Yiting Huang, Wei J Nanobiotechnology Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02211-8. BioMed Central 2023-11-15 /pmc/articles/PMC10652587/ /pubmed/37968657 http://dx.doi.org/10.1186/s12951-023-02211-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Senrui
Cheng, Shengwen
Chen, Bowen
Xiao, Pengcheng
Zhan, Jingdi
Liu, Jiacheng
Chen, Zhuolin
Liu, Junyan
Zhang, Tao
Lei, Yiting
Huang, Wei
Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis
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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652587/
https://www.ncbi.nlm.nih.gov/pubmed/37968657
http://dx.doi.org/10.1186/s12951-023-02211-8
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