title: Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro.
abstract: OBJECTIVE
  To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs) could be maintained in serum from acute-on-chronic liver failure (ACLF) patients.
  
  
  METHODS
  Hepatocyte supportive functions and cytotoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evaluated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture, respectively. Chemokine profile was also examined for the normal serum and liver failure serum.
  
  
  RESULTS
  Hepatocyte growth factor (HGF) and Tumor necrosis factor; tumor necrosis factor (TNF)-α were remarkably elevated in response to ACLF while epidermal growth factor (EGF) and VEGF levels were significantly decreased. Liver failure serum samples induced a higher detachment rate, lower viability and decreased liver support functions in the homo-hepatocyte culture. Hepatocytes co-cultured with MSCs could tolerate the cytotoxicity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cultured with healthy human serum in vitro. In addition, co-cultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum.
  
  
  CONCLUSIONS
  ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Shi
authors.forename: Jin-Yang
authors.initials: JY
authors.lastname: Gu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Jiang-Qiang
authors.initials: JQ
authors.lastname: Xiao
authors.forename: Xian-Wen
authors.initials: XW
authors.lastname: Yuan
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D058625:End Stage Liver Disease / Q000097:blood*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D044967:Serum; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor