The hepatic stellate cells as potential regional hepatic progenitor cells

Background/AimWide spread of liver diseases and low efficacy of their treatment require to search new ways for solving this problem. The identification and application of hepatic progenitor cell can be one of the promising... [ view full abstract ]

Background/Aim

Wide spread of liver diseases and low efficacy of their treatment require to search new ways for solving this problem. The identification and application of hepatic progenitor cell can be one of the promising methods. Because the hepatic stellate cells (HSC) produce important morphogenic cytokines and express stem cell markers, the aim of our study is to check the possibility of hepatocyte differentiation of HSC.

Materials/Methods

We studied immunohisto- and cytochemically the phenotype of HSC: 1) during rat and human prenatal development; 2) during liver regeneration after partial hepatectomy (PH) or damage with lead nitrate; 3) in pure culture and in culture with addition of FGF and HGF; 4) after transplantation of HSC transfected with Green Fluorescent Protein (GFP) into intact rats and rats after PH.

Results

We found that HSC expressed stem cell markers both during the first trimester of human gestation (Bcl-2) and liver regeneration in rats (C-kit). Moreover they were cytokeratin18+/cytokeratin19+ in the embryonic period and after formation of monolayer in culture too. Growth factors in culture intensified and accelerated the appearance of cytokeratins, a-Fetoprotein and Hepatocyte Specific Antigen in HSC. At last we observed the GFP+ hepatocytes in rat’s livers after transplantation of GFP-transfected HSC to them. Transplantation of HSC into rats after PH resulted in a significant increase of homing and stimulation of their differentiation into hepatocytes-like cells.

Conclusions

We conclude that HSC can be hepatic progenitor cells and can be used for elaboration of stem cell therapy methods in hepatology.