Recipient-derived hepatocytes in sex-mismatched liver allografts after liver transplantation: early versus late transplant biopsies.
BACKGROUND
The presence of microchimerism in transplanted tissues is well defined; however, the timeframe of appearance and disappearance of engraftment in liver allograft is unknown. The aims of this study were to analyze for the presence of "recipient-derived cells" in sex-mismatched individuals after liver transplantation, comparing the frequency of "recipient-derived cell repopulation" in early versus late transplant biopsies and to evaluate the relationship between "recipient-derived cell repopulation" and the severity of graft injury.


METHODS
Paraffin-embedded liver biopsy samples of 18 recipients were reviewed. Sixteen of them were obtained from recipients with sex-mismatched donors. The remaining two were obtained from recipients with sex-matched donors and were used as controls. Immunohistochemistry and fluorescence in situ hybridization double-labeling method were performed on pretreated slides using anti-human hepatocyte antibody to identify hepatocytes, a mouse anti-human cytokeratin-7 to identify ductal epithelial cells, and using CEPX/Y DNA probes for visualizing X and Y chromosomes. The double-labeled slides were examined systematically using an image analyzer system.


RESULTS
The mean time from transplantation to biopsy was 8.1 months. Eleven of the 16 samples obtained from recipients with sex-mismatched grafts demonstrated "recipient-derived hepatocyte repopulation," comprising a mean of 2.1% of the hepatocytes. In the control biopsies, none of the cells demonstrated different nuclear signals from the donor's sex origin. The presence and proportion of "recipient-derived hepatocyte repopulation" rate were significantly higher in early transplant biopsies than in late transplant biopsies (P < 0.05).


CONCLUSIONS
Some hepatocytes of sex-mismatched liver grafts were replaced by "recipient-derived cells" during injury. Such repopulation is more common in the early liver-graft biopsies. The severity of acute cellular rejection appears to have no effect on the rate of recipient-derived repopulation.
Idilman
Ramazan
R
Department of Gastroenterology, Ankara University School of Medicine, Ibn'i Sina Hospital, Sihhiye, Ankara, Turkey 06100. idilman@dailup.ankara.edu.tr
Erden
Esra
E
Kuzu
Isnsu
I
Ersoz
Sadik
S
Karasu
Zeki
Z
Karayalcin
Kaan
K
Yuce
Gul
G
Tokat
Yaman
Y
Sahin
Yasemin
Y
Tukun
Ajlan
A
Akarca
Ulus S
US
Karayalcin
Selim
S
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002459:Cell Fusion; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology; D014184:Transplantation, Homologous