Therapeutic potential of propagated hepatocyte transplantation in liver failure

J Surg Res. 2011 May 1;167(1):e29-37. doi: 10.1016/j.jss.2010.12.008. Epub 2011 Jan 7.

Abstract

Background: This study aimed to evaluate the therapeutic potential of intrasplenic transplantation of culture-propagated homologous hepatocytes in rats suffering from acute liver failure (ALF).

Methods: ALF was induced in dipeptidyl peptidase IV-negative (DPPIV(-)) Fischer 344 rats by totally removing the two anterior liver lobes (68% of the liver) and ligating the pedicle of the right lobe (24% of the liver). Hepatocytes isolated from DPPIV(+) Fischer 344 rats were cultured for 11 d to propagate 3-fold, and the resulting hepatocytes were dubbed "culture-propagated hepatocytes (CPHEPs)". A total of 1.5 × 10(7) cells of CPHEPs were transplanted intrasplenically before ALF induction (CPHEP group). Similarly, freshly isolated hepatocytes (FIHEPs) were transplanted as a positive control (FIHEP group), and culture medium (CM) was injected into rats as a negative control (CM group).

Results: The survival of the CPHEP group was comparable to that of the FIHEP group and longer than that of the CM group (P < 0.01). Both CPHEP and FIHEP transplantation improved blood parameters such as ammonia, total bilirubin, glutamic pyruvic transaminase, and glutamic oxaloacetic transaminase; transplantation also affected liver tissue parameters such as apoptosis rate and bromodeoxyuridine-labeling index.

Conclusions: Transplantation of culture-propagated homologous hepatocytes has a remarkable therapeutic potential for ALF in rats.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Cell Transplantation / methods*
  • Cells, Cultured
  • Dipeptidyl Peptidase 4 / adverse effects
  • Hepatocytes / cytology
  • Hepatocytes / transplantation*
  • Liver / physiopathology
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / mortality
  • Liver Failure, Acute / therapy*
  • Models, Animal
  • Rats
  • Rats, Inbred F344
  • Treatment Outcome

Substances

  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Dipeptidyl Peptidase 4