Therapeutic evaluation of a microbioartificial liver with recombinant HepG2 cells for rats with hepatic failure

Expert Opin Biol Ther. 2013 Nov;13(11):1507-13. doi: 10.1517/14712598.2013.843666. Epub 2013 Sep 27.

Abstract

Background: HepG2/(ArgI+OTC)4 (previously constructed) is a recombinant human liver cell line with a strong ability to reduce ammonia in vitro. However, its application value ex vivo has not been investigated.

Objectives: To examine the efficacy of HepG2/(ArgI+OTC)4 cells in a micro-bioartificial liver (micro-BAL) device for application ex vivo.

Methods: A simple micro-BAL device containing a microbioreactor and a small-type peristaltic pump was installed. The rats with hepatic failure were randomly divided into three groups (n = 10) and were treated with different micro-BAL loaded HepG2/(ArgI+OTC)4 cells, HepG2 cells and control (without cells), respectively. Changes in the liver and kidney function of the rats were determined before and after the treatment. The lifespan of the rats were observed and recorded.

Results: Despite the difference in survival time between experimental groups of rat model was not statistically significant, the capacity of HepG2/(ArgI+OTC)4 cells treatment group for tolerance and detoxifying ammonia was increased much more than that of HepG2 cells (p < 0.05), and other biochemical indicators of HepG2/(ArgI+OTC)4 cells treatment group were also better than that of HepG2 cells treatment group (p < 0.05).

Conclusions: HepG2/(ArgI+OTC)4 cells can provide a better biological support for rats with hepatic failure in a short period of time, and they may be used as a convenient and useful choice for further cell material research of BAL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonia / metabolism*
  • Animals
  • Arginase / genetics
  • Arginase / metabolism
  • Arginase / therapeutic use*
  • Bioreactors
  • Galactosamine / toxicity
  • Hep G2 Cells / metabolism*
  • Humans
  • Implants, Experimental
  • Infusion Pumps, Implantable
  • Liver Failure / blood
  • Liver Failure / chemically induced
  • Liver Failure / pathology
  • Liver Failure / surgery*
  • Liver, Artificial*
  • Male
  • Miniaturization
  • Ornithine-Oxo-Acid Transaminase / genetics
  • Ornithine-Oxo-Acid Transaminase / metabolism
  • Ornithine-Oxo-Acid Transaminase / therapeutic use*
  • Oxidation-Reduction
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / therapeutic use
  • Urea / metabolism

Substances

  • Recombinant Fusion Proteins
  • Galactosamine
  • Ammonia
  • Urea
  • Ornithine-Oxo-Acid Transaminase
  • ARG1 protein, human
  • Arginase