Injury-dependent retention of intraportally administered mesenchymal stromal cells following partial hepatectomy of steatotic liver does not lead to improved liver recovery

PLoS One. 2013 Jul 18;8(7):e69092. doi: 10.1371/journal.pone.0069092. Print 2013.

Abstract

The aim of this study was to evaluate the effect of bone marrow-derived mesenchymal stromal cell (BM-MSC) administration on liver function following partial hepatectomy (PHx) of methionine/choline-deficient (MCD) diet induced steatotic livers in rodents. Here we identified and validated serum cholinesterase (CHE) and triglyceride (TG) levels as non-invasive markers to longitudinally monitor rat liver function. Using in vivo bioluminescence imaging, retention of BM-MSC in the liver was observed following intraportal administration, but not after intravenous administration. Therefore, BM-MSC were intraportally delivered to investigate the effect on liver recovery and/or regeneration after PHx. However, despite recovery to normal body weight, liver weight and NAS score, both serum CHE and TG levels of non-treated and cell-treated rats with PHx after MCD diet remained significantly lower as compared to those of control rats. Importantly, serum CHE levels, but not TG levels, of cell-treated rats remained significantly lower as compared to those of non-treated rats, thereby warranting that certain caution should be considered for future clinical application of IP BM-MSC administration in order to promote liver regeneration and/or function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Biomarkers / blood*
  • Body Weight
  • Choline Deficiency
  • Cholinesterases / blood
  • DNA Primers / genetics
  • Fatty Liver / etiology
  • Fatty Liver / physiopathology*
  • Fatty Liver / surgery*
  • Female
  • Flow Cytometry
  • Hepatectomy / methods
  • Immunophenotyping
  • Liver Regeneration / physiology*
  • Luminescent Measurements
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Methionine / deficiency
  • Organ Size
  • Rats
  • Rats, Inbred Lew
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / blood

Substances

  • Biomarkers
  • DNA Primers
  • Triglycerides
  • Methionine
  • Cholinesterases

Grants and funding

This work was supported by a BOF-NOI 2009 research grant from the University of Antwerp (granted to DY and KDG). NB holds a PhD-studentship from the Flemish Institute for Science and Technology (IWT-Vlaanderen). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.