However, the generation of this chimeric humanized mouse requires advanced technical skills and the scarcity of adequate human primary material remains a significant logistical challenge.[41, 42] Selleckchem CYC202 Our model showed in the present study is easy to create, and it has Ag-specific T-cell exhaustion and Ag persistent in the liver seen in chronic HCV patients. These features suggest that this system is useful for therapeutic HCV vaccine development. THIS WORK WAS supported by grants from a Saitama Medical University Internal Grant (24-A-1-01 and 24-B-1-06), Grant from Ochiai Memorial Award 2011 and the Ministry of Health, Labor, and Welfare, Japan. The authors thank Hiroe Akatsuka
for technical assistance. “
“Considerable progress has been made in developing antifibrotic agents and other strategies to treat liver fibrosis; however, significant long-term restoration of functional liver mass has not yet been achieved. Therefore, we investigated whether transplanted hepatic stem/progenitor cells can effectively repopulate Navitoclax ic50 the liver with advanced fibrosis/cirrhosis. Stem/progenitor cells derived from fetal livers or mature hepatocytes
from DPPIV+ F344 rats were transplanted into DPPIV− rats with thioacetamide (TAA)-induced fibrosis/cirrhosis; rats were sacrificed 1, 2, or 4 months later. Liver tissues were analyzed by histochemistry, hydroxyproline determination, reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. After chronic TAA administration, DPPIV− F344 rats exhibited progressive fibrosis, cirrhosis, and severe hepatocyte damage. Besides stellate cell activation, increased numbers of stem/progenitor cells (Dlk-1+, AFP+, CD133+, Sox-9+, FoxJ1+) were observed. In conjunction with partial hepatectomy (PH), transplanted stem/progenitor cells engrafted, proliferated competitively compared to host hepatocytes, differentiated into hepatocytic and biliary
epithelial cells, and generated new liver mass with extensive long-term liver repopulation (40.8 ± 10.3%). Remarkably, more than 20% liver repopulation was achieved in the absence of PH, associated with reduced fibrogenic activity (e.g., expression of alpha smooth muscle actin, platelet-derived selleck products growth factor receptor β, desmin, vimentin, tissue inhibitor of metalloproteinase-1) and fibrosis (reduced collagen). Furthermore, hepatocytes can also replace liver mass with advanced fibrosis/cirrhosis, but to a lesser extent than fetal liver stem/progenitor cells. Conclusion: This study is a proof of principle demonstration that transplanted epithelial stem/progenitor cells can restore injured parenchyma in a liver environment with advanced fibrosis/cirrhosis and exhibit antifibrotic effects. (Hepatology 2014;58:284–295) Chronic liver disease with cirrhosis is the twelfth leading cause of death in the United States.