Differentiation of murine marrow megakaryocyte progenitors (CFUm): humoral control in vitro.

Differentiation of mouse marrow megakaryocyte progenitors (CFUm) was studied in vitro by a colony assay using a plasma clot system. Erythropoietin (EPO) from sheep plasma (6 units/mg protein) in doses from 1 to 5 units/ml induced a linear increase in CFUm to a maximum of 20 colonies/10(5) cells plated. Human urinary EPO also induced a dose-responsive increase in CFUm, but the maximum was 9 colonies/10(5) with 2.0 units/ml of EPO and there was a decrease in colonies above that concentration. Thrombocytopoiesis-stimulating factor (TSF) derived from human embryonic kidney culture supernatant fluids induced a dose-responsive increase in CFUm in concentrations from 0.01 to 0.32 mg protein/ml in the absence of added EPO. TSF did not support the growth in vitro of erythroid colonies from mouse marrow (CFUe and BFUe) indicating the absence of EPO activity. In these studies sheep EPO appeared more effective in supporting CFUe growth than human EPO. TSF also had a stimulatory function in megakaryocyte differentiation at a precursor level. Multiple humoral factors play a role in megakaryocytopoiesis in vitro.