Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

Abstract

This chapter provides novel information about the survival features of hepatic resident stem/progenitor cells (NG2+ HSPs) during liver fibrosis/cirrhotic development. A well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhotic/cancer mouse model was developed to evaluate the fate of the HSPs and its clinical implications. This model possess three time-zones during the disease development: fibrosis (3–5 weeks post-DEN), cirrhosis (6–10 weeks post-DEN), and cancers (up to 10 weeks post-DEN). During this process, the model represents histological patterns similar to those described in humans and shows better survival of the HSPs in the fibrotic zone, which was correlated with inflammatory signals, as compared to the cirrhotic zone. It has also been discovered that immune CD8+ T cells in the fibrotic zone are beneficial in liver fibrosis resolution, suggesting that the fibrotic time zone is important for mobilizing endogenous HSPs and cell-based therapy. As such, we hypothesize that clinical strategies in fibrotic/cirrhotic liver treatment are necessary either in time at the fibrotic phase or to adopt an approach of regulating HSP viability when the disease develops into the cirrhotic phase.