Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Protect Liver Ischemia/Reperfusion Injury by Reducing CD154 Expression on CD4+ T Cells via CCT2

Jun Zheng; Tongyu Lu; Chaorong Zhou; Jianye Cai; Xiaomei Zhang; Jinliang Liang; Xin Sui; Xiaoyan Chen; Liang Chen; Yao Sun; Jiebin Zhang; Wenjie Chen; Yingcai Zhang; Jia Yao; Guihua Chen; Yang Yang

doi:10.1002/advs.201903746

Advanced Science (Sep 2020)

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Protect Liver Ischemia/Reperfusion Injury by Reducing CD154 Expression on CD4+ T Cells via CCT2

Jun Zheng,
Tongyu Lu,
Chaorong Zhou,
Jianye Cai,
Xiaomei Zhang,
Jinliang Liang,
Xin Sui,
Xiaoyan Chen,
Liang Chen,
Yao Sun,
Jiebin Zhang,
Wenjie Chen,
Yingcai Zhang,
Jia Yao,
Guihua Chen,
Yang Yang

Affiliations

Jun Zheng: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Tongyu Lu: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Chaorong Zhou: Department of Hepatic Surgery and Liver Transplantation Center The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Jianye Cai: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Xiaomei Zhang: Organ Transplantation Research Center of Guangdong Province Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutes The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Jinliang Liang: Organ Transplantation Research Center of Guangdong Province Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutes The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Xin Sui: Surgical ICU The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Xiaoyan Chen: Biological Treatment Center The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Liang Chen: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Yao Sun: Surgical ICU The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Jiebin Zhang: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Wenjie Chen: Biological Treatment Center The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Yingcai Zhang: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Jia Yao: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Guihua Chen: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China
Yang Yang: Department of Hepatic Surgery and Liver Transplantation Center, Guangdong Key Laboratory of Liver Disease Research Guangdong Province Engineering Laboratory for Transplantation Medicine The Third Affiliated Hospital of Sun Yat‐sen University 600 Tianhe Road Guangzhou 510630 China

DOI: https://doi.org/10.1002/advs.201903746
Journal volume & issue: Vol. 7, no. 18
pp. n/a – n/a

Abstract

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Abstract As a cause of postoperative complications and early hepatic failure after liver transplantation, liver ischemia/reperfusion injury (IRI) still has no effective treatment during clinical administration. Although the therapeutic potential of mesenchymal stem cells (MSCs) for liver IRI has been previously shown, the underlying mechanisms are not completely clear. It is accepted that MSC‐derived extracellular vesicles (MSC‐EVs) are newly uncovered messengers for intercellular communication. Herein, it is reported that umbilical cord‐derived MSCs (UC‐MSCs) improve liver IRI in mice through their secreted EVs. It is also visualized that UC‐MSC‐EVs mainly concentrate in liver after 6 h of reperfusion. Furthermore, UC‐MSC‐EVs are found to significantly modulate the membranous expression of CD154 of intrahepatic CD4+ T cells, which is an initiation of inflammatory response in liver and can aggravate liver IRI. Mechanistically, protein mass spectrum analysis is performed and it is revealed that Chaperonin containing TCP1 subunit 2 (CCT2) enriches in UC‐MSC‐EVs, which regulates the calcium channels to affect Ca2+ influx and suppress CD154 synthesis in CD4+ T cells. In conclusion, these results highlight the therapeutic potential of UC‐MSC‐EVs in attenuating liver IRI. This finding suggests that CCT2 from UC‐MSC‐EVs can modulate CD154 expression of intrahepatic CD4+ T cells during liver IRI through the Ca2+‐calcineurin‐NFAT1 signaling pathway.

Published in Advanced Science

ISSN: 2198-3844 (Online)
Publisher: Wiley
Country of publisher: Germany
LCC subjects: Science
Website: https://onlinelibrary.wiley.com/journal/21983844

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