Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice
Abstract Background The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional h...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2016-10-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-016-1051-1 |
| _version_ | 1818497804211847168 |
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| author | Shanzheng Lu Ganggang Shi Xiaoxi Xu Grace Wang Xu Lan Peng Sun Xiang Li Baoren Zhang Xiangying Gu Thomas E. Ichim Hao Wang |
| author_facet | Shanzheng Lu Ganggang Shi Xiaoxi Xu Grace Wang Xu Lan Peng Sun Xiang Li Baoren Zhang Xiangying Gu Thomas E. Ichim Hao Wang |
| author_sort | Shanzheng Lu |
| collection | DOAJ |
| description | Abstract Background The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)–induced acute liver injury (ALI). Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects. |
| first_indexed | 2024-12-10T18:49:55Z |
| format | Article |
| id | doaj.art-2ce12a981b7d49f08ae2f62040557b2c |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-10T18:49:55Z |
| publishDate | 2016-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2ce12a981b7d49f08ae2f62040557b2c2022-12-22T01:37:21ZengBMCJournal of Translational Medicine1479-58762016-10-0114111510.1186/s12967-016-1051-1Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in miceShanzheng Lu0Ganggang Shi1Xiaoxi Xu2Grace Wang3Xu Lan4Peng Sun5Xiang Li6Baoren Zhang7Xiangying Gu8Thomas E. Ichim9Hao Wang10Department of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Medical University General HospitalFaculty of Medicine, University of TorontoDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Affiliated Hospital of Weifang Medical UniversityDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of Gynecology and Obstetrics, Tianjin Medical University General HospitalImmune Advisors LLCDepartment of General Surgery, Tianjin Medical University General HospitalAbstract Background The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)–induced acute liver injury (ALI). Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.http://link.springer.com/article/10.1186/s12967-016-1051-1Endometrial regenerative cellsAcute liver injuryAnti-inflammatoryImmunoregulation |
| spellingShingle | Shanzheng Lu Ganggang Shi Xiaoxi Xu Grace Wang Xu Lan Peng Sun Xiang Li Baoren Zhang Xiangying Gu Thomas E. Ichim Hao Wang Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice Journal of Translational Medicine Endometrial regenerative cells Acute liver injury Anti-inflammatory Immunoregulation |
| title | Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice |
| title_full | Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice |
| title_fullStr | Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice |
| title_full_unstemmed | Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice |
| title_short | Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice |
| title_sort | human endometrial regenerative cells alleviate carbon tetrachloride induced acute liver injury in mice |
| topic | Endometrial regenerative cells Acute liver injury Anti-inflammatory Immunoregulation |
| url | http://link.springer.com/article/10.1186/s12967-016-1051-1 |
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