Human Amnion Epithelial Cell Therapy for Chronic Liver Disease

Figure 1

Overview of chronic hepatic wound healing and fibrosis. Necrotic and/or apoptotic hepatocytes release their cell content stimulating monocyte infiltration and hepatic stellate cell activation. Upon infiltration, monocytes differentiate into proinflammatory Ly6C^hi macrophages which, along with resident Kupffer cells, release a myriad of proinflammatory and profibrotic cytokines. These factors promote additional inflammatory cell recruitment, regulate tissue repair, and activate hepatic stellate cells. Activated stellate cells transdifferentiate into ECM-producing myofibroblasts. Myofibroblasts also augment ECM remodelling by producing TIMPs and regulate tissue repair by secreting inflammatory and profibrotic factors. As a consequence of liver inflammation, T cells are recruited which further promote inflammation and/or stellate cell activation through cytokine production. Finally, persistent hepatic inflammation, ECM remodelling, and hepatocyte injury activate the liver progenitor cell compartment. Liver progenitor cells proliferate and differentiate into hepatocytes to assist liver regeneration during CLD. CLD perpetuates this wound healing response resulting in persistent liver inflammation and the development of fibrosis.