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
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
Search for more papers by this authorToshiaki Nakano
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
Search for more papers by this authorKuang-Tzu Huang
Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan
Search for more papers by this authorChien-Chih Chen
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorKuang-Den Chen
Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan
Search for more papers by this authorChia-Yun Lai
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
Search for more papers by this authorShih-Ming Yang
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
Search for more papers by this authorChih-Che Lin
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
Search for more papers by this authorChih-Chi Wang
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
Search for more papers by this authorYu-Fan Cheng
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
Search for more papers by this authorKing-Wah Chiu
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
Search for more papers by this authorYur-Ren Kuo
Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Shigeru Goto
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
Correspondence: Professor Shigeru Goto or Professor Chao-Long Chen Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan. Email: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Chao-Long Chen
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
Correspondence: Professor Shigeru Goto or Professor Chao-Long Chen Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan. Email: [email protected]; [email protected]Search for more papers by this authorLi-Wen Hsu
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
Search for more papers by this authorToshiaki Nakano
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
Search for more papers by this authorKuang-Tzu Huang
Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan
Search for more papers by this authorChien-Chih Chen
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorKuang-Den Chen
Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung, Taiwan
Search for more papers by this authorChia-Yun Lai
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
Search for more papers by this authorShih-Ming Yang
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
Search for more papers by this authorChih-Che Lin
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
Search for more papers by this authorChih-Chi Wang
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
Search for more papers by this authorYu-Fan Cheng
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
Search for more papers by this authorKing-Wah Chiu
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
Search for more papers by this authorYur-Ren Kuo
Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Shigeru Goto
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
Correspondence: Professor Shigeru Goto or Professor Chao-Long Chen Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan. Email: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Chao-Long Chen
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
Correspondence: Professor Shigeru Goto or Professor Chao-Long Chen Liver Transplantation Program and Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan. Email: [email protected]; [email protected]Search for more papers by this authorAbstract
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 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.
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.
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