BACKGROUND: ''Bone marrow-derived stem cells'' have attracted great attention as potential candidates for liver-directed gene therapy and as a tool for regenerative medicine. However, the fate of these cells is not well-known. The aim of this present study was to investigate the fate of ''recipient-derived repopulated hepatocytes'' in sex-mismatched liver allografts in individuals following liver transplantation during systematic longitudinally performed liver biopsies. METHODS: Paraffin-embedded sex-mismatched liver biopsy samples of nine recipients (male/female ratio 5/4; mean age: 39.7 yr) were reviewed. Double labeling with immunohistochemistry for hepatocytes and recipient-specific bone marrow-derived cells and fluorescence in-situ hybridization for visualizing X and Y chromosomes were performed. These slides were examined systematically using an image analyzer system (Olympus microscope; Cyto-Vision, Applied Imaging, Biosciences Centre, Newcastle, UK). Only cells with two nuclear spots were considered for interpretation. RESULTS: The mean times from transplantation to first biopsy and between the first and the second biopsies were 5.9 and 20.9 months respectively. The proportion of recipient-derived repopulated hepatocytes was significantly decreased in the late biopsies when compared with the early biopsies (p = 0.001). All nine samples of the first biopsies had demonstrated recipient-derived hepatocyte repopulation, with a mean of 2.0%, whereas only seven of nine samples of the second biopsies had demonstrated recipient-derived hepatocyte repopulation with a low mean of 0.5% (p = 0.001). CONCLUSION: Based on these results, we suggest that ''recipient-specific bone marrow-derived hepatocyte repopulation'' in liver allograft during tissue injury is a relatively early event.
BACKGROUND: ''Bone marrow-derived stem cells'' have attracted great attention as potential candidates for liver-directed gene therapy and as a tool for regenerative medicine. However, the fate of these cells is not well-known. The aim of this present study was to investigate the fate of ''recipient-derived repopulated hepatocytes'' in sex-mismatched liver allografts in individuals following liver transplantation during systematic longitudinally performed liver biopsies. METHODS:Paraffin-embedded sex-mismatched liver biopsy samples of nine recipients (male/female ratio 5/4; mean age: 39.7 yr) were reviewed. Double labeling with immunohistochemistry for hepatocytes and recipient-specific bone marrow-derived cells and fluorescence in-situ hybridization for visualizing X and Y chromosomes were performed. These slides were examined systematically using an image analyzer system (Olympus microscope; Cyto-Vision, Applied Imaging, Biosciences Centre, Newcastle, UK). Only cells with two nuclear spots were considered for interpretation. RESULTS: The mean times from transplantation to first biopsy and between the first and the second biopsies were 5.9 and 20.9 months respectively. The proportion of recipient-derived repopulated hepatocytes was significantly decreased in the late biopsies when compared with the early biopsies (p = 0.001). All nine samples of the first biopsies had demonstrated recipient-derived hepatocyte repopulation, with a mean of 2.0%, whereas only seven of nine samples of the second biopsies had demonstrated recipient-derived hepatocyte repopulation with a low mean of 0.5% (p = 0.001). CONCLUSION: Based on these results, we suggest that ''recipient-specific bone marrow-derived hepatocyte repopulation'' in liver allograft during tissue injury is a relatively early event.
Authors: X Hu; T Okabayashi; A M Cameron; Y Wang; M Hisada; J Li; L C Raccusen; Q Zheng; R A Montgomery; G M Williams; Z Sun Journal: Am J Transplant Date: 2016-02-26 Impact factor: 8.086
Authors: Zhaoli Sun; Xiuying Zhang; Jayme E Locke; Qizhi Zheng; Shingo Tachibana; Anna Mae Diehl; George Melville Williams Journal: Hepatology Date: 2009-02 Impact factor: 17.425