Reconstitution of Mice with Modified Liver Stem Cells

Hepatic progenitor cells isolated from fetal liver can be transplanted into recipient mice to reconstitute an organ system. Retroviral infection can be used to introduce putative oncogenes or short-hairpin RNAs (shRNAs) targeting putative tumor suppressors into the cells; reconstituted mice then develop livers that are chimeric for cells bearing a specific alteration. This approach has the advantage of examining tumorigenesis on a largely wild-type background (if only a subset of cells are infected), a situation that more accurately parallels the human situation. Additionally, tumor development occurs within the appropriate native microenvironment. Here, we describe the isolation of hepatic progenitor cells, as well as the reconstitution and tumor monitoring of recipient mice.