In a Rat Model of Acute Liver Failure, Icaritin Improved the Therapeutic Effect of Mesenchymal Stem Cells by Activation of the Hepatocyte Growth Factor/c-Met Pathway
| Autor: | Dong-yong Lv, Zheng-Zheng Zhang, Han-yu Wang, Shu Li, Weihong Kuang, Juan Zeng, Lu Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
C-Met
Article Subject medicine.medical_treatment Liver transplantation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation In vivo parasitic diseases medicine 030304 developmental biology 0303 health sciences business.industry Mesenchymal stem cell Stem-cell therapy lcsh:Other systems of medicine lcsh:RZ201-999 Complementary and alternative medicine chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research Hepatocyte growth factor business medicine.drug Research Article |
| Zdroj: | Evidence-Based Complementary and Alternative Medicine, Vol 2019 (2019) Evidence-based Complementary and Alternative Medicine : eCAM |
| ISSN: | 1741-4288 |
| Popis: | Acute liver failure (ALF) is a serious life-threatening condition. Mesenchymal stem cells (MSCs) may be an effective treatment for this condition and a good alternative to liver transplantation. Icaritin (ICT) is an active ingredient of the genus Epimedium, a traditional Chinese medicine, with the potential to enhance the proliferation of MSCs. The purpose of this study was to explore whether ICT increased the therapeutic effects of MSCs and explore its underlying mechanisms. For in vivo experiments, a rat ALF model was established by intraperitoneal injection of D(+)-galactosamine/ lipopolysaccharide. MSCs cocultured with ICT were used to treat ALF rats and the protective effects assessed as survival rate, levels of serum AST and ALT, and histological changes in liver tissue. For in vitro experiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study demonstrated that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications. |
| Databáze: | OpenAIRE |
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