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Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model

Researchers increasingly report the therapeutic effect of exosomes derived from rat bone marrow mesenchymal stem cells (Exos-rBMMSC) on liver disease, while the optimal dose of Exos-rBMMSC in liver cirrhotic treatment has not been reported. In this study, we aimed to explore the efficacy and dose of...

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Autores principales: Zhang, Yichi, Zhangdi, Hanjing, Nie, Xinsheng, Wang, Lijuan, Wan, Zhuzhi, Jin, Hao, Pu, Ronghui, Liang, Meihui, Chang, Yuan, Gao, Yang, Zhang, Hailong, Jin, Shizhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776579/
https://www.ncbi.nlm.nih.gov/pubmed/36552767
http://dx.doi.org/10.3390/cells11244004
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author Zhang, Yichi
Zhangdi, Hanjing
Nie, Xinsheng
Wang, Lijuan
Wan, Zhuzhi
Jin, Hao
Pu, Ronghui
Liang, Meihui
Chang, Yuan
Gao, Yang
Zhang, Hailong
Jin, Shizhu
author_facet Zhang, Yichi
Zhangdi, Hanjing
Nie, Xinsheng
Wang, Lijuan
Wan, Zhuzhi
Jin, Hao
Pu, Ronghui
Liang, Meihui
Chang, Yuan
Gao, Yang
Zhang, Hailong
Jin, Shizhu
author_sort Zhang, Yichi
collection PubMed
description Researchers increasingly report the therapeutic effect of exosomes derived from rat bone marrow mesenchymal stem cells (Exos-rBMMSC) on liver disease, while the optimal dose of Exos-rBMMSC in liver cirrhotic treatment has not been reported. In this study, we aimed to explore the efficacy and dose of Exos-rBMMSC in a hepatic cirrhosis rat model. The therapeutic effects of a low dose, medium dose and high dose of Exos-rBMMSC were assessed by liver function tests and histopathology. After four-weeks of Exos-rBMMSC therapy, pyroptosis-related expression levels in the medium dose and the high dose Exos-rBMMSC groups were significantly decreased compared to those in the liver cirrhosis group (p < 0.05). The hepatic function assay and histopathology results showed significant improvement in the medium dose and the high dose Exos-rBMMSCs groups. The localization of PKH67-labeled Exos-rBMMSC was verified microscopically, and these particles were coexpressed with the PCNA, NLRP3, GSDMD and Caspase-1. Our results demonstrated that Exos-rBMMSC accelerated hepatocyte proliferation and relieved liver fibrosis by restraining hepatocyte pyroptosis. More importantly, we confirmed that the high dose of Exos-rBMMSC may be the optimal dose for liver cirrhosis, which is conducive to the application of Exos-rBMMSC as a promising cell-free strategy.
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spelling pubmed-97765792022-12-23 Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model Zhang, Yichi Zhangdi, Hanjing Nie, Xinsheng Wang, Lijuan Wan, Zhuzhi Jin, Hao Pu, Ronghui Liang, Meihui Chang, Yuan Gao, Yang Zhang, Hailong Jin, Shizhu Cells Article Researchers increasingly report the therapeutic effect of exosomes derived from rat bone marrow mesenchymal stem cells (Exos-rBMMSC) on liver disease, while the optimal dose of Exos-rBMMSC in liver cirrhotic treatment has not been reported. In this study, we aimed to explore the efficacy and dose of Exos-rBMMSC in a hepatic cirrhosis rat model. The therapeutic effects of a low dose, medium dose and high dose of Exos-rBMMSC were assessed by liver function tests and histopathology. After four-weeks of Exos-rBMMSC therapy, pyroptosis-related expression levels in the medium dose and the high dose Exos-rBMMSC groups were significantly decreased compared to those in the liver cirrhosis group (p < 0.05). The hepatic function assay and histopathology results showed significant improvement in the medium dose and the high dose Exos-rBMMSCs groups. The localization of PKH67-labeled Exos-rBMMSC was verified microscopically, and these particles were coexpressed with the PCNA, NLRP3, GSDMD and Caspase-1. Our results demonstrated that Exos-rBMMSC accelerated hepatocyte proliferation and relieved liver fibrosis by restraining hepatocyte pyroptosis. More importantly, we confirmed that the high dose of Exos-rBMMSC may be the optimal dose for liver cirrhosis, which is conducive to the application of Exos-rBMMSC as a promising cell-free strategy. MDPI 2022-12-10 /pmc/articles/PMC9776579/ /pubmed/36552767 http://dx.doi.org/10.3390/cells11244004 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Yichi
Zhangdi, Hanjing
Nie, Xinsheng
Wang, Lijuan
Wan, Zhuzhi
Jin, Hao
Pu, Ronghui
Liang, Meihui
Chang, Yuan
Gao, Yang
Zhang, Hailong
Jin, Shizhu
Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model
title Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model
title_full Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model
title_fullStr Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model
title_full_unstemmed Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model
title_short Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model
title_sort exosomes derived from bmmscs mitigate the hepatic fibrosis via anti-pyroptosis pathway in a cirrhosis model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776579/
https://www.ncbi.nlm.nih.gov/pubmed/36552767
http://dx.doi.org/10.3390/cells11244004
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