Rat liver biliary epithelial cells support long-term production of haemopoietic progenitors from human CD34 cells

In this study we report the supportive activity of rat liver epithelial cells (RLEC) on human haemopoiesis in the absence of exogeneously supplied growth factors. RLEC is a rat cell line derived from primitive biliary cells with epithelial characteristics which induce the long-term differentiation of hepatocytes through cell-cell contacts. We have established the ability of these cells to sustain long-term survival and multilineage differentiation of human haemopoietic progenitors from unfractionated bone marrow and growth-factor mobilized peripheral blood cells, and from human CD34+ and CD34+ CD38- haemopoietic cells, with a higher efficiency than the murine MS-5 stromal cell line: the numbers of committed progenitors recovered from RLEC cocultures after 8 weeks were 3-fold higher than from MS-5 cocultures, with an unusually high BFU-E production. Furthermore, using diffusible insert cultures, we demonstrated that, despite the lack of strong adhesive interaction between haemopoietic cells and RLEC, physical proximity was absolutely required for optimum stimulation of LTC-IC by RLEC. Taken together, these results show that biliary epithelial cells support human haemopoiesis and cause speculation that common mechanisms might be used by RLEC to regulate both the hepatocyte and the haemopoietic progenitors differentiation.