EFFECTS OF CONTINUOUS STEM-CELL FACTOR ADMINISTRATION ON NORMAL AND ERYTHROPOIETIN-STIMULATED MURINE HEMATOPOIESIS - EXPERIMENTAL RESULTS AND MODEL ANALYSIS

The aim of this study was to determine how stem cell factor (SCF) modi fies hemopoietic cell production. First we determined the effects of a prolonged SCP administration on murine hemopoiesis and analyzed the r esults by a mathematical simulation model of hemopoiesis in order to e xplain the data. Subsequently we investigated the effects of simultane ous coadministration of SCF + erythropoietin (Epo), to see how effects of early and late cytokines superimpose. SCF administration during 14 days induced a proliferative wave through the hemopoietic system; col ony forming units-granulocyte macrophage (CFU-GM), burst forming units -erythroid (BFU-E) and colony forming units erythroid (CFU-E) were the first to be augmented, followed by their respective progeny, ultimate ly leading to increased blood cell numbers. Despite continued treatmen t most cell numbers returned to normal values in 14 days. colony formi ng units-spleen (CFU-S), however, remained elevated. This wave pattern could be explained within the framework of a previously established m athematical model of hemopoiesis, if it was assumed that SCF affected the cycling status of primitive cells and if regulatory feedback loops of erythroid and myeloid progenitors on these cells were also allowed . Simultaneous SCF and Epo administration led to synergistic effects o n CFU-E numbers and hematocrit values at moderate Epo doses. At high E po doses, however, this was less pronounced. We conclude that SCF incr eases the input into committed hemopoietic lineages, where late acting cytokines can induce further amplification.