Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice.
OBJECTIVE
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 (alpha-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 alpha-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.


CONCLUSIONS
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.
Zheng
Jin-Fang
JF
Department of Hepatobiliary Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Liang
Li-Jian
LJ
Wu
Chang-Xiong
CX
Chen
Jin-Song
JS
Zhang
Zhen-Sheng
ZS
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004052:Diethylnitrosamine / Q000009:adverse effects; D004847:Epithelial Cells / Q000637:transplantation*; D005260:Female; D006498:Hepatectomy; D006820:Hyaluronic Acid / Q000097:blood; D007797:Laminin / Q000097:blood; D008099:Liver / Q000196:embryology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000601:surgery*; D051379:Mice; D008807:Mice, Inbred BALB C; D033581:Stem Cell Transplantation; D014185:Transplantation, Isogeneic
D007797:Laminin; D004052:Diethylnitrosamine; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase