Hepatic progenitor cell represents a transitioning cell population between liver epithelium and stroma

Abstract Following an acute injury, the liver may maintain its structure and function through mitotic division of mature hepatocytes (i.e. hepatic regeneration). However, the regeneration ability of hepatocytes can be impaired in chronic liver diseases including chronic viral infection and alcohol abuse. Hepatic progenitor cells/oval cells (HPCs/OCs), capable of differentiation into both hepatocytes and cholangiocytes, occur and proliferate during chronic injury. Unfortunately, a use of HPCs for clinical therapy is blocked by the difficulty of exact identity of HPCs in liver. Focusing on the links between phenotype of HPCs and real stem cells originating from fetal liver or bone marrow (BM), the recent studies of HPCs neglect functional analysis and the close relationship between activation of HPCs and extracellular matrix (ECM) remodeling. It is currently widely accepted that mesenchymal-epithelial transition (EMT) and epithelial-mesenchymal transition (MET) play important roles not only in liver development but also in healing of chronic injured adult liver. Co-expression of epithelial/mesenchymal and HPCs markers has been demonstrated in cells undergoing EMT/MET. These cells led to hepatic regeneration after transplanted into rats with chronic liver injury. Notably, there is an increased expression of mesenchymal markers in HPCs after exposure to transforming growth factor-beta1 (TGF-β1). Based on these evidences, we hypothesize that HPCs represent a transitioning cell population undergoing EMT/MET, both parenchymal and mesenchymal cells of liver may be the direct sources of HPCs.