Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 7, 2006; 12(45): 7292-7298
Published online Dec 7, 2006. doi: 10.3748/wjg.v12.i45.7292
Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice
Jin-Fang Zheng, Li-Jian Liang, Chang-Xiong Wu, Jin-Song Chen, Zhen-Sheng Zhang
Jin-Fang Zheng, Li-Jian Liang, Department of Hepatobiliary Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Jin-Fang Zheng, Chang-Xiong Wu, Jin-Song Chen, Zhen-Sheng Zhang, Department of Hepatobiliary Surgery, the People’s Hospital of Hainan Province, Haikou 570311, Hainan Province, China
Supported by the Natural Science Foundation of Hainan Province, No. 805107
Correspondence to: Dr. Li-Jian Liang, Department of Hepa-tobiliary Surgery, the First Affiliated Hospital, Sun Yat-Sen University, No. 74 Zhongshan Road II, Guangzhou 510080, Guangdong Province, China. lianglj@medmail.com.cn
Telephone: +86-20-87755766-8096 Fax: +86-20-87755766
Received: August 9, 2006
Revised: August 28, 2006
Accepted: September 16, 2006
Published online: December 7, 2006
Abstract

AIM: To investigate the effect of transplanted fetal liver epithelial progenitor (FLEP) cells on liver fibrosis in mice.

METHODS: FLEP cells were isolated from embryonal day (ED) 14 BALB/c mice and transplanted into female syngenic BALB/c mice (n = 60). After partial hepatectomy (PH), diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received FLEP cells and non-supplemented drinking water, the model group received DEN-spiked water, and the experimental group received FLEP cells and DEN. Mice were killed after 1, 2, and 3 mo, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), and laminin (LN) in serum, and hydroxyproline (Hyp) content in liver were assessed. Alpha-smooth muscle actin (α-SMA) of liver was tested by immunohistochemistry. Transplanted male mice FLEP cells were identified by immunocytochemistry for sry (sex determination region for Y chromosome) protein.

RESULTS: Serum ALT, AST, HA, and LN were markedly reduced by transplanted FLEP cells. Liver Hyp content and α-SMA staining in mice receiving FLEP cells were lower than that of the model group, which was consistent with altered liver pathology. Transplanted cells proliferated and differentiated into hepatocytes and bile duct epithelial cells with 30%-50% repopulation in the liver fibrosis induced by DEN after 3 mo.

CONCLUSION: Transplanted FLEP cells proliferate and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the fiberized liver induced by DEN, which restores liver function and reduces liver fibrosis.

Keywords: Fetal liver; Epithelial progenitor cells; Cell therapy; Proliferation; Liver fibrosis