Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration.
OBJECTIVE
To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration.


METHODS
Human hepatic parenchymal and stromal components and phenotypic changes of human cells during liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry.


RESULTS
ISH analysis demonstrated human Alu-positive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)(+), CD34(+) and CD45(+) cells were observed in the chimeric liver on day 10 after PHx-induced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver.


CONCLUSIONS
HRC liver provides a tool for investigating human liver regeneration in a humanized animal model.
Sun
Yan
Y
Institute of Comparative Medicine and Center of Experimental Animals, Southern Medical University, Guangzhou, Guangdong Province, China.
Xiao
Dong
D
Li
Hong-An
HA
Jiang
Jin-Fang
JF
Li
Qing
Q
Zhang
Ruo-Shuang
RS
Chen
Xi-Gu
XG
D020087:Alu Elements; D000818:Animals; D049109:Cell Proliferation; D006498:Hepatectomy; D006801:Humans; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration; D010641:Phenotype; D051381:Rats; D018183:Transplantation Chimera