title: Prolonged survival by combined treatment with granulocyte colony-stimulating factor and dipeptidyl peptidase IV inhibitor in a rat small-for-size liver transplantation model.
abstract: OBJECTIVE
  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 2 μg/kg per day starting 5 days prior to transplantation. G-CSF was combined with the p.o. administration of a DPP-IV inhibitor (2 mg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.
authors.forename: Kuang-Tzu
authors.initials: KT
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.
authors.forename: Kuang-Den
authors.initials: KD
authors.lastname: Chen
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Che
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Chi
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: King-Wah
authors.initials: KW
authors.lastname: Chiu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Yur-Ren
authors.initials: YR
authors.lastname: Kuo
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.affiliation: Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan.|Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
keywords: dipeptidyl peptidase IV inhibitor; granulocyte colony-stimulating factor; hepatic lineage cells; liver transplantation; small-for-size liver graft syndrome