Bone marrow-derived mesenchymal stem cells inhibits hepatocyte apoptosis after acute liver injury

Int J Clin Exp Pathol. 2015 Jan 1;8(1):107-16. eCollection 2015.

Abstract

Objective: To investigate the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on acute liver injury (ALI) rats.

Material and methods: BMSCs were extracted from rat bone marrow, cultured and expansion in vitro, and identified by flow cytometer. Rat model with acute liver injury was established by employing D-galactosamine and Lipopolysaccharide. Male rats were randomly divided into ALI model group and BMSCs transplantation group. Rats were sacrificed 24 h, 72 h and 120 h after BMSCs injection to determine alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction (RT-PCR) of α-fetoprotein (AFP) and glypican-3 (GPC3) were performed to analysis proliferation. Terminal deoxynucleontidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assays were used to analyze apoptosis and mitochondria-dependent-pathway related factors Bax and Bcl-2 were examined by Western blot.

Results: Compared with the ALI model group, the BMSCs transplantation group presented the lower levels of ALT, AST, decreased Bax proteins expression, and increased Bcl-2 expression. The mRNA levels of AFP and GPC3 and expression of PCNA were significantly higher in BMSCs transplantation group.

Conclusions: BMSCs transplantation could significantly restore liver function. These effects were supposed to be mediated by suppressing hepatocyte apoptosis as well as promoting proliferation. Reduction of apoptosis seemed to correlate with mitochondria-dependent-pathway.

Keywords: Bone marrow-derived mesenchymal stem cells; acute liver injury; apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Blotting, Western
  • Disease Models, Animal
  • Hepatocytes / pathology*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Liver Failure, Acute / pathology*
  • Liver Function Tests
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction