1. Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model.
- Author
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Zhang, Yichi, Zhangdi, Hanjing, Nie, Xinsheng, Wang, Lijuan, Wan, Zhuzhi, Jin, Hao, Pu, Ronghui, Liang, Meihui, Chang, Yuan, Gao, Yang, Zhang, Hailong, and Jin, Shizhu
- Subjects
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HEPATIC fibrosis , *LIVER cells , *EXOSOMES , *MESENCHYMAL stem cells , *CIRRHOSIS of the liver , *LIVER function tests , *LIVER diseases - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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