Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro

World J Gastroenterol. 2011 May 21;17(19):2397-406. doi: 10.3748/wjg.v17.i19.2397.

Abstract

Aim: 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.

Conclusion: ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.

Keywords: Acute-on-chronic liver failure serum; Bone marrow marrow mesenchymal stem cells; Co-culture; Hepatocyte-based modality; Primary hepatocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coculture Techniques
  • End Stage Liver Disease / blood*
  • Epidermal Growth Factor / metabolism
  • Female
  • Hepatocyte Growth Factor / metabolism
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver Failure, Acute / blood*
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Serum*
  • Swine
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor