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http://dx.doi.org/10.14348/molcells.2019.2283

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p  

Lu, Feng-Bin (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Chen, Da-Zhi (Department of Gastroenterology, The First Hospital of Peking University)
Chen, Lu (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Hu, En-De (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Wu, Jin-Lu (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Li, Hui (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Gong, Yue-Wen (College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba)
Lin, Zhuo (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Wang, Xiao-Dong (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Li, Ji (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Jin, Xiao-Ya (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Xu, Lan-Man (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Chen, Yong-Ping (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology)
Publication Information
Molecules and Cells / v.42, no.12, 2019 , pp. 906-918 More about this Journal
Abstract
MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.
Keywords
autoimmune liver disease; exosomes; immunomodulatory; mesenchymal stromal cells;
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