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Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice
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 hepatocyt...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075169/ https://www.ncbi.nlm.nih.gov/pubmed/27770815 http://dx.doi.org/10.1186/s12967-016-1051-1 |
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author | Lu, Shanzheng Shi, Ganggang Xu, Xiaoxi Wang, Grace Lan, Xu Sun, Peng Li, Xiang Zhang, Baoren Gu, Xiangying Ichim, Thomas E. Wang, Hao |
author_facet | Lu, Shanzheng Shi, Ganggang Xu, Xiaoxi Wang, Grace Lan, Xu Sun, Peng Li, Xiang Zhang, Baoren Gu, Xiangying Ichim, Thomas E. Wang, Hao |
author_sort | Lu, Shanzheng |
collection | PubMed |
description | 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 (CCl(4))–induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl(4). 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 CCl(4) induction. RESULTS: ERC treatment effectively decreased the CCl(4)-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. |
format | Online Article Text |
id | pubmed-5075169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50751692016-10-27 Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice Lu, Shanzheng Shi, Ganggang Xu, Xiaoxi Wang, Grace Lan, Xu Sun, Peng Li, Xiang Zhang, Baoren Gu, Xiangying Ichim, Thomas E. Wang, Hao J Transl Med Research 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 (CCl(4))–induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl(4). 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 CCl(4) induction. RESULTS: ERC treatment effectively decreased the CCl(4)-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. BioMed Central 2016-10-22 /pmc/articles/PMC5075169/ /pubmed/27770815 http://dx.doi.org/10.1186/s12967-016-1051-1 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Lu, Shanzheng Shi, Ganggang Xu, Xiaoxi Wang, Grace Lan, Xu Sun, Peng Li, Xiang Zhang, Baoren Gu, Xiangying Ichim, Thomas E. Wang, Hao Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice |
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 | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075169/ https://www.ncbi.nlm.nih.gov/pubmed/27770815 http://dx.doi.org/10.1186/s12967-016-1051-1 |
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