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

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Abstract

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.

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