BOVINE FETAL-LIVER STROMAL CELLS SUPPORT ERYTHROID COLONY FORMATION -ENHANCEMENT BY INSULIN-LIKE GROWTH-FACTOR-II

Stromal cells are one of the components of the hematopoietic microenvi ronment, which is crucial for the proliferation and differentiation of hematopoietic cells. We have obtained a bovine fetal-liver stromal ce ll line that supports erythroid colony formation in the presence of er ythropoietin. The cells are cytokeratin-negative and vimentin-positive , indicating a mesenchymal origin. Furthermore, they have phagocytic a ctivity and show endothelial-like morphology. Erythropoietin at a conc entration of 2 mU/mL was sufficient to increase erythropoiesis in the presence of these stromal cells, and the effect could be further enhan ced in the presence of physiological concentrations of insulin-like gr owth factor II. The supportive role of stromal cells on erythroid colo ny formation could still be observed, although to a lesser extent, whe n the erythroid precursors were physically separated from the stromal monolayer by an agar layer or with serum-free media conditioned by str omal cells. Ultrafiltration of the conditioned media indicated that th e active factors have a nominal molecular weight smaller than 3 kD, wh ich does not correspond to any of the known cytokines with erythroid-c ell stimulating activities. Our data suggest that these fetal-liver st romal cells play an important role in fetal erythropoiesis, a function which was previously thought to be played exclusively by fetal hepato cytes.