Megakaryocytopoiesis and platelet production: does stem cell factor play a role?

Megakaryocytopoiesis, resulting in the production and release of platelets, is a multistage procession of cellular differentiation and maturation which is regulated by a constellation of cytokines. Since thrombocytopenia is a frequent dose-limiting toxicity of chemotherapy, newly-identified cytokines have been actively investigated for their potential megakaryocyte/platelet-promoting properties. Stem cell factor (SCF, also known as mast cell growth factor, Steel factor or Kit ligand) has been found to synergize with GM-CSF, IL-6, IL-3, IL-11 or Epo to increase the numbers of megakaryocyte-containing colonies (i.e., CFU-Meg, BFU-Meg, CFU-GMM, CFU-GEMM). On the other hand, SCF increased the number of megakaryocytes per colony in the presence of IL-3, GM-CSF or IL-6. SCF also stimulated the proliferation of specific megakaryocytic cell lines (i.e., CMK, M-07e). SCF did not, however, alter megakaryocyte markers or increase cell ploidy. Thus, SCF appears to expand the committed myeloid progenitor compartments, rather than increase the rate of megakaryocyte maturation or the number of platelets released. We describe studies in which SCF stimulated murine CFU-Meg alone and in the presence of IL-3. However, a decrease in cultured cell plating density resulted in ablation of this SCF-stimulation of CFU-Meg colonies. CFU-Meg colony stimulation by SCF was dose dependent, even under serum-free conditions. The effects of SCF in other in vitro and in vivo animal model systems are reviewed.