Title: Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia‐reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response
Abstract: The FASEB JournalVolume 33, Issue 2 p. 1695-1710 ResearchFree to Read Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response Jia Yao, Jia Yao Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaThese authors contributed equally to this work.Search for more papers by this authorJun Zheng, Jun Zheng Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaThese authors contributed equally to this work.Search for more papers by this authorJianye Cai, Jianye Cai Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaThese authors contributed equally to this work.Search for more papers by this authorKaining Zeng, Kaining Zeng Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorChaorong Zhou, Chaorong Zhou Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorJiebin Zhang, Jiebin Zhang Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorShihui Li, Shihui Li Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorHui Li, Hui Li Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorLiang Chen, Liang Chen Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorLiying He, Liying He Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou, ChinaSearch for more papers by this authorHuaxin Chen, Huaxin Chen Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorHongyuan Fu, Hongyuan Fu Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorQi Zhang, Qi Zhang Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorGuihua Chen, Guihua Chen Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorYang Yang, Corresponding Author Yang Yang [email protected] Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected] Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected]Search for more papers by this authorYingcai Zhang, Corresponding Author Yingcai Zhang [email protected] Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected] Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected]Search for more papers by this author Jia Yao, Jia Yao Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaThese authors contributed equally to this work.Search for more papers by this authorJun Zheng, Jun Zheng Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaThese authors contributed equally to this work.Search for more papers by this authorJianye Cai, Jianye Cai Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaThese authors contributed equally to this work.Search for more papers by this authorKaining Zeng, Kaining Zeng Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorChaorong Zhou, Chaorong Zhou Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorJiebin Zhang, Jiebin Zhang Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorShihui Li, Shihui Li Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorHui Li, Hui Li Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorLiang Chen, Liang Chen Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorLiying He, Liying He Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou, ChinaSearch for more papers by this authorHuaxin Chen, Huaxin Chen Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorHongyuan Fu, Hongyuan Fu Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorQi Zhang, Qi Zhang Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorGuihua Chen, Guihua Chen Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaSearch for more papers by this authorYang Yang, Corresponding Author Yang Yang [email protected] Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected] Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected]Search for more papers by this authorYingcai Zhang, Corresponding Author Yingcai Zhang [email protected] Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Research Center of Guangdong Province, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Liver Disease Research, Key Laboratory of Liver Disease Biotherapy and Translational Medicine, Guangdong Higher Education Institutes, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected] Correspondence: Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, No. 600 Tianhe Rd., Tianhe District, Guangzhou, Guangdong Province 510630, China. E-mail: [email protected]Search for more papers by this author First published: 18 September 2018 https://doi.org/10.1096/fj.201800131RRCitations: 9 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL ABSTRACT Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on immunoregulation, tissue repair, and regeneration from the bench to the bedside. Increasing evidence demonstrates that extracellular vesicles (EVs) derived from MSCs could contribute to these effects and are considered as a potential replacement for stem cell-based therapies. However, the efficacy and underlying mechanisms of EV-based treatment in hepatic ischemia-reperfusion injury (IRI) remain unclear. Here, we demonstrated that human umbilical cord MSC-EVs (huc-MSC-EVs) could protect against IRI-induced hepatic apoptosis by reducing the infiltration of neutrophils and alleviating oxidative stress in hepatic tissue in vivo. Meanwhile, huc-MSC-EVs reduced the respiratory burst of neutrophils and prevented hepatocytes from oxidative stress-induced cell death in vitro. Interestingly, we found that the mitochondria-located antioxidant enzyme, manganese superoxide dismutase (MnSOD), was encapsulated in huc-MSC-EVs and reduced oxidative stress in the hepatic IRI model. Knockdown of MnSOD in huc-MSCs decreased the level of MnSOD in huc-MSC-EVs and attenuated the antiapoptotic and antioxidant capacities of huc-MSC-EVs, which could be partially rescued by MnSOD mimetic manganese (III) 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP). In summary, these findings provide new clues to reveal the therapeutic effects of huc-MSC-EVs on hepatic IRI and evaluate their preclinical application.—Yao, J., Zheng, J., Cai, J., Zeng, K., Zhou, C., Zhang, J., Li, S., Li, H., Chen, L., He, L., Chen, H., Fu, H., Zhang, Q., Chen, G., Yang, Y., Zhang, Y. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. FASEB J. 33, 1695–1710 (2019). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2fj201800131rr-sup-0001.docxapplication/docx, 4.6 MB Supplementary Material 1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume33, Issue2February 2019Pages 1695-1710 RelatedInformation
Publication Year: 2018
Publication Date: 2018-09-18
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 151
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