Effects of insulin-like growth factor I, platelet-derived growth factor, fibroblast growth factor, and transforming growth factor-beta on thymidine incorporation into fetal liver cells

We have studied the effect of different growth factors on thymidine incorporation in cell cultures of erythroid cells from fetal calf and rat livers, a system which has been used in the past as a bioassay for the purification of erythropoietin and erythropoietin-like factors. Insulin-like growth factor I significantly stimulated thymidine incorporation in calf and rat liver cells. Its action in both cell types was practically identical to the effect of bovine serum erythrotropin, a peptide structurally similar to insulin-like growth factor II. The synergistic effect between insulin-like growth factor I and erythropoietin could be observed with partially purified sheep plasma erythropoietin but not with recombinant human erythropoietin. The highest thymidine incorporation was observed when both erythropoietin and insulin-like growth factor I were added simultaneously. Platelet-derived growth factor had a lower thymidine incorporation-stimulating activity than insulin-like growth factor and did not have any synergistic effect with erythropoietin in rat liver cells. Fibroblast growth factor (0.4-6.0 ng/ml) was completely inactive in the thymidine incorporation assay of calf liver cells. Transforming growth factor-beta alone at a concentration of 1 ng/ml significantly inhibited thymidine incorporation into rat liver cells. It seems that from all growth factors tested so far, those belonging to the insulin family of peptides are the most likely to be detected in the thymidine incorporation assays using calf or rat liver cells.