title: Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice.
abstract: 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).
  
  
  
  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 CCl4induction.
  
  
  
  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.
  
  
  
  Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.
authors: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.|Tianjin General Surgery Institute, Tianjin, China.
authors: Shanzheng
authors: S
authors: Lu
authors: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.|Tianjin General Surgery Institute, Tianjin, China.
authors: Ganggang
authors: G
authors: Shi
authors: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.|Tianjin General Surgery Institute, Tianjin, China.
authors: Xiaoxi
authors: X
authors: Xu
authors: Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors: Grace
authors: G
authors: Wang
authors: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.|Tianjin General Surgery Institute, Tianjin, China.
authors: Xu
authors: X
authors: Lan
authors: Department of General Surgery, Affiliated Hospital of Weifang Medical University, Shandong, China.
authors: Peng
authors: P
authors: Sun
authors: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.|Tianjin General Surgery Institute, Tianjin, China.
authors: Xiang
authors: X
authors: Li
authors: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.|Tianjin General Surgery Institute, Tianjin, China.
authors: Baoren
authors: B
authors: Zhang
authors: Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.
authors: Xiangying
authors: X
authors: Gu
authors: Immune Advisors LLC, San Diego, CA, 92121, USA.
authors: Thomas E
authors: TE
authors: Ichim
authors: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. hwangca272@hotmail.com.|Tianjin General Surgery Institute, Tianjin, China. hwangca272@hotmail.com.
authors: Hao
authors: H
authors: Wang
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002251:Carbon Tetrachloride; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004717:Endometrium / Q000166:cytology* / Q000637:transplantation*; D005260:Female; D022781:Hepatocytes / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000276:immunology / Q000293:injuries* / Q000473:pathology* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009930:Organic Chemicals / Q000378:metabolism; D012038:Regeneration; D013154:Spleen / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D009930:Organic Chemicals; C070080:PKH 26; D002251:Carbon Tetrachloride
keywords: Acute liver injury; Anti-inflammatory; Endometrial regenerative cells; Immunoregulation