Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Aug 7, 2009; 15(29): 3611-3620
Published online Aug 7, 2009. doi: 10.3748/wjg.15.3611
Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration
Yan Sun, Dong Xiao, Hong-An Li, Jin-Fang Jiang, Qing Li, Ruo-Shuang Zhang, Xi-Gu Chen
Yan Sun, Dong Xiao, Institute of Comparative Medicine and Center of Experimental Animals, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Yan Sun, Dong Xiao, Xi-Gu Chen, Cancer Research Institute, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Hong-An Li, Jin-Fang Jiang, Department of Pathology, Shihezi University, Shihezi 832002, Xinjiang Uygur Autonomous Region, China
Qing Li, Institute of Gynecology and Obstetrics, the Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, Guangdong Province, China
Ruo-Shuang Zhang, Xi-Gu Chen, Center of Experimental Animals, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Sun Y and Xiao D contributed equally to this work; Sun Y, Xiao D and Chen XG conceived and designed the experiments; Sun Y and Xiao D performed primary experiments; Li HA and Jiang JF performed immunohistochemistry; Li Q performed in situ hybridization; Zhang RS performed animal experiments; Sun Y and Xiao D collected, analyzed and interpreted the data and wrote the manuscript.
Correspondence to: Xi-Gu Chen, Professor, Cancer Research Institute, Southern Medical University, Guangzhou 510515, Guangdong Province, China. xiguchen1516@yahoo.com.cn
Telephone: +86-20-33151566
Fax: +86-20-87331230
Received: May 25, 2009
Revised: June 30, 2009
Accepted: July 7, 2009
Published online: August 7, 2009
Abstract

AIM: 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.

CONCLUSION: HRC liver provides a tool for investigating human liver regeneration in a humanized animal model.

Keywords: Human-rat chimera; Humanized liver; Human hepatocyte-like cells; Humanized hepatic functional unit; Partial hepatectomy model; Liver regeneration