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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
Sumario: | 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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