Transplant of Hepatocytes, Undifferentiated Mesenchymal Stem Cells, and In Vitro Hepatocyte-Differentiated Mesenchymal Stem Cells in a Chronic Liver Failure Experimental Model: A Comparative Study

Exp Clin Transplant. 2018 Feb;16(1):81-89. doi: 10.6002/ect.2016.0226. Epub 2017 Jun 5.

Abstract

Objectives: Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure.

Materials and methods: Undifferentiated human cord blood mesenchymal stem cells were isolated, pro-pagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocyte-like cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepato-genically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed.

Results: Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undifferentiated mesenchymal stem cell-treated group.

Conclusions: Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Carbon Tetrachloride
  • Cell Differentiation*
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Chemical and Drug Induced Liver Injury / surgery*
  • Cord Blood Stem Cell Transplantation*
  • End Stage Liver Disease / chemically induced
  • End Stage Liver Disease / pathology
  • End Stage Liver Disease / physiopathology
  • End Stage Liver Disease / surgery*
  • Hepatocytes / metabolism
  • Hepatocytes / transplantation*
  • Humans
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / pathology
  • Liver Cirrhosis, Experimental / physiopathology
  • Liver Cirrhosis, Experimental / surgery*
  • Liver Regeneration
  • Liver Transplantation / methods*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells* / metabolism
  • Mice, Inbred BALB C
  • Phenotype
  • Rats, Inbred Lew
  • Recovery of Function
  • Time Factors

Substances

  • Biomarkers
  • Carbon Tetrachloride