Prolonged survival by combined treatment with granulocyte colony-stimulating factor and dipeptidyl peptidase IV inhibitor in a rat small-for-size liver transplantation model

Li Wen Hsu, Toshiaki Nakano, Kuang Tzu Huang, Chien Chih Chen, Kuang Den Chen, Chia Yun Lai, Shih Ming Yang, Chih Che Lin, Chih Chi Wang, Yu Fan Cheng, King Wah Chiu, Yur Ren Kuo, Shigeru Goto*, Chao Long Chen

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations

Abstract

Aim: Despite the great advances and excellent outcomes of liver transplantation (LT), small-for-size (SFS) graft syndrome is a life-threatening complication that remains to be overcome. In the present study, we investigated the therapeutic effect of combined treatment with granulocyte colony-stimulating factor (G-CSF) and a dipeptidyl peptidase IV (DPP-IV) inhibitor on SFS liver graft syndrome. Methods: The transplantation of small-sized Lewis donor livers into green fluorescent protein (GFP) transgenic Wistar rats was performed and the recipients were randomly assigned to one of four groups (without treatment, DPP-IV inhibitor treatment, G-CSF treatment and G-CSF/DPP-IV inhibitor combination). Recombinant human G-CSF was injected s.c. at a dose of 2μg/kg per day starting 5 days prior to transplantation. G-CSF was combined with the p.o. administration of a DPP-IV inhibitor (2mg/kg per day) after transplantation until the end of the observation period. Results: The post-transplant survival and liver function of rats treated with G-CSF/DPP-IV inhibitor combination therapy were significantly improved with an increased number of recipient-derived GFP positive cells into the liver grafts. A confocal microscopy study showed cytokeratin (CK)-18 and GFP positive hepatic progenitor cells in the parenchyma of the liver allografts. Untreated rats and rats treated with either G-CSF or DPP-IV inhibitor did not exhibit the prolonged survival and had less GFP and CK-18 positive cells in the liver grafts after SFS LT. Conclusion: Our results suggest that combined treatment with G-CSF and DPP-IV inhibitor may synergistically induce migration and differentiation of recipient-derived stem cells into the hepatic progenitor cells, resulting in the amelioration of SFS liver graft syndrome.

Original languageEnglish
Pages (from-to)804-813
Number of pages10
JournalHepatology Research
Volume45
Issue number7
DOIs
StatePublished - 01 07 2015

Bibliographical note

Publisher Copyright:
© 2014 The Japan Society of Hepatology.

Keywords

  • Dipeptidyl peptidase IV inhibitor
  • Granulocyte colony-stimulating factor
  • Hepatic lineage cells
  • Liver transplantation
  • Small-for-size liver graft syndrome

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