Precise cell therapy for liver fibrosis: Endothelial cell and macrophage therapy

Liver fibrosis is typically caused by chronic viral hepatitis and, more recently, fatty liver disease associated with obesity. There are currently no approved drugs for liver cirrhosis, and liver transplantation is limited by donor scarcity, thus driving the investigation of novel therapeutic strategies. The development of liver fibrosis presents with stage- and zone-dependent characteristics that manifest as distinct dynamic changes during vascularization and extracellular matrix (ECM) deposition. However, current cellular therapies do not consider the spatiotemporal variations of liver fibrosis without identifying the precise location and stage to administer the intervention to achieve optimal therapeutic effects. Herein, we focus on endothelial cell (EC) and macrophage therapy for liver fibrosis because of their important roles in regulating the spatiotemporal changes of vascularization and ECM deposition during liver fibrosis progression. Overall, this review summarizes the stage-dependent EC and macrophage therapy for liver fibrosis, elucidates their respective mechanisms, and exemplifies potential strategies to realize precise cell therapy by targeting specific liver zones.