This application proposes to use NOD/SCID mice transplanted (intrasplenically or under kidney capsule) with human hepatocytes for HCV infection. The project will first identify hepatocyte subpopulations that are most susceptible to HCV infection, and examine the possible effects of hepatocyte growth factor (HGF) on hepatocyte growth in the transplanted mice. The same approach will also be applied to fumarylacetoacetate hydrolase (FAH) mice to enrich transplanted human hepatocytes. For all of the optimization procedures, hepatitis delta virus (HDV) will be used as a surrogate virus for HCV. Eventually, these humanized mice will be tested for HCV infections.
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Xiong, Anming; Austin, Timothy W; Lagasse, Eric et al. (2008) Isolation of human fetal liver progenitors and their enhanced proliferation by three-dimensional coculture with endothelial cells. Tissue Eng Part A 14:995-1006 |