The fate of recipient-derived hepatocytes in sex-mismatched liver allograft following liver transplantation

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.