Hepatocytic differentiation of hepatic progenitor cells in acute and chronic hepatocytic human liver diseases.

Hepatocytes are the cells that normally shoulder the burden of regeneration after liver damage. However, when loss of hepatocytes is massive, or combined with inhibition of proliferative capacity of mature hepatocytes, activation of a dormant compartment of intrahepatic progenitor cells occurs. Hepatic progenitor cells (HPCs) can differentiate towards either hepatocytes or bile duct epithelial cells based on impaired mature cell type. Upon transit amplification, HPCs generate new hepatocytes (via the formation of intermediate hepatocytes) and biliary cells to restore liver homeostasis. Thus, these cells provide a cell-based therapeutic alternative to organ transplant, the current treatment of choice for end-stage liver diseases. Most data refer to the canals of Hering as the niche for HPCs. The niche is a special microenvironment composed of cells, extracellular matrix and soluble factors released by the niche cells that help to maintain the characteristics of the progenitor cells. The interaction between different components of HPC niche is thought to be the key factor in regulating the self renewal maintenance and differentiation capacity of the HPCs. Despite a partial elucidation of the mechanisms governing hepatic progenitor cell activation and differentiation in experimental rodent models, very little is known about the human hepatic progenitor cell niche and its signals. For the aim of this project, hepatic progenitor cells as well as intermediate hepatocytes (in the way of differentiation towards mature hepatocytes) from patients with -acute and chronic hepatocytic diseases were captured by laser capture microdissection and their gene expression profiles are being compared by microarrays and RT-PCR. Gene expression profiling of this microdissected material gives us insight into the pathways of activation and hepatocytic differentiation of HPCs. The results will guide a detailed immunohistochemical study of the protein expression based on the up- or down-regulated mRNA levels. By this way we hope that we will be able to elucidate, even a small part, of the complex signalling pathways involved in the differentiation and maturation of human HPCs towards mature hepatocyte.

Keywords:Liver diseases

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences