Endothelial cell impact on hepatic progenitor cells

Introduction Hepatic stem cell populations have been demonstrated from embryonic stages through adulthood. During embryonic development the endodermal stem cells interact with adjacent endothelial cells. Hypothesis We propose that a model to recapitulate embryonic liver development, focusing on cellular interactions between endothelial and hepatic progenitor cells (HPC), would provide insights into proliferation and differentiation of HPC. Methods An endothelial cell line was cultured with HPC at 83,000 cells/cm 2 . The system was analyzed for proliferation using an MTT assay and differentiation by RT‐PCR looking at hepatocyte markers albumin and AFP and CK19, a biliary marker. Results 1) The HPC/endothelial cell co‐culture demonstrated accelerated formation of HPC colonies with colony development occurring 3 days earlier than control. 2) There were no differences in the proliferation rate between co‐cultured cells and controls. 3) RT‐PCR demonstrated that HPC in co‐culture undergo differentiation earlier than controls. Conclusion By simulating conditions of organogenesis we have shown enhanced proliferation and differentiation of HPC. This data validates our endothelial cell/HPC co‐culture as a viable model for studying HPC proliferation and differentiation. Research supported by NIH 5‐T32‐GM008450‐12 (MHW) & DK059302 (DAG).