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Serum from Acute-on-chronic Liver Failure Patients May Affect Mesenchymal Stem Cells Transplantation by Impairing the immunosuppressive Function of Cells

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Journal of Clinical and Translational Hepatology 2021年第4期9卷 503-513页

作者： Yongyuan Zheng Shu Zhu Xingrong Zheng Wenxiong Xu Xuejun Li Jianguo Li Zhiliang Gao Chan Xie Liang Peng Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Province Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Background and Aims:The safety and efficacy of mesenchymal stem cells(MSCs)in the treatment of acute-onchronic liver failure(ACLF)have been ***,the impact of the pathological ACLF microenvironment on MSCs is less well *** study was designed to explore the changes in the functional properties of MSCs exposed to ACLF ***:MSCs were cultured in the presence of 10%,30%and 50%serum concentrations from ACLF patients and healthy ***,the cell morphology,phenotype,apoptosis and proliferation of MSCs were evaluated,including the immunosuppressive ***,mRNA sequencing analysis was used to identify the molecules and pathways involved in MSC functional changes in the context of ***:In the presence of ACLF serum,MSC morphology significantly changed but phenotype did ***,MSC proliferation activity was weakened,while the apoptosis rate was lightly *** importantly,the immunosuppressive function of MSCs was enhanced in a lowconcentration serum environment but transformed into a proinflammatory response in a high-concentration serum *** sequencing indicated that 10%serum concentration from ACLF patients mediated the PI3K-Akt pathway to enhance the anti-inflammatory effect of MSCs,while the 50%serum concentration from ACLF patients promoted the conversion of MSCs into a proinflammatory function by affecting the cell ***:The 50%ACLF serum concentration is more similar to the environment in the human body,which means that direct peripheral blood intravenous infusion of MSCs may reduce the effect of *** treatments of plasma exchange to reduce harmful substances in serum may promote MSCs to exert a stronger anti-inflammatory effect.

关键词： Mesenchymal stem cells Acute-on-chronic liver failure immu-nomodulatory Cell therapy Microenvironment

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