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

Molecules and Cells 2019년 42권 12호 p.906 ~ 918
 ( Lu Feng-Bin ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases

 ( Chen Da-Zhi ) - Peking University First Hospital Department of Gastroenterology
 ( Chen Lu ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Hu En-De ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Wu Jin-Lu ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Li Hui ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Gong Yue-Wen ) - University of Manitoba Rady Faculty of Health Sciences College of Pharmacy
 ( Lin Zhuo ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Wang Xiao-Dong ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Li Ji ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Jin Xiao-Ya ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Xu Lan-Man ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases
 ( Chen Yong-Ping ) - Wenzhou Medical University First Affiliated Hospital Department of Infectious Diseases

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.

키워드

autoimmune liver disease; exosomes; immunomodulatory; mesenchymal stromal cells
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