Thrombopoietin requires additional megakaryocyte-active cytokines for optimal ex vivo expansion of megakaryocyte precursor cells. Blood

Little is known concerning the interaction of thrombopoietin (TPO) with other megakaryocyte-active cytokines in direct-ing the early events of megakaryocyte development. Culture of CD341 cells in interleukins (IL)-1,-6,-11, plus stem cell factor (SCF; S) results in a 10- to 12-fold expansion in total cell numbers, whereas total CD411 megakaryocytes are expanded D120-fold over input levels. Addition of TPO to IL-1,-6,-11, S generates a biphasic proliferation of CD411 cells, accelerates their rate of production, and results in an ex vivo expansion of more than 200-fold. The addition of Flt-3 ligand (FL) increases CD411 cell expansion to D380-fold over input levels. In the absence of TPO, D95 % of the expanded cells show the phenotype of promegakaryoblasts; TPO and/or FL addition increases CD41 antigen density and ploidy in a subpopulation of promegakaryoblasts. A moderate (approxi