MEGAKARYOCYTOPOIESIS AND PLATELET PRODUCTION - DOES STEM-CELL FACTOR PLAY A ROLE

Megakaryocytopoiesis, resulting in the production and release of plate lets, is a multistage procession of cellular differentiation and matur ation which is regulated by a constellation of cytokines. Since thromb ocytopenia is a frequent dose-limiting toxicity of chemotherapy, newly -identified cytokines have been actively investigated for their potent ial megakaryocyte/platelet-promoting properties. Stem cell factor (SCF , also known as mast cell growth factor, Steel factor or Kit ligand) h as been found to synergize with GM-CSF, IL-6, IL-3, IL-11 or Epo to in crease the numbers of megakaryocyte-containing colonies (i.e., CFU-Meg , BFU-Meg, CFU-GMM, CFU-GEMM). On the other hand, SCF increased the nu mber of megakaryocytes per colony in the presence of IL-3, GM-CSF or I L-6. SCF also stimulated the proliferation of specific megakaryocytic cell lines (ie., CMK, M-07e). SCF did not, however, alter megakaryocyt e markers or increase cell ploidy. Thus, SCF appears to expand the com mitted myeloid progenitor compartments, rather than increase the rate of megakaryocyte maturation or the number of platelets released. We de scribe studies in which SCF stimulated murine CFU-Meg alone and in the presence of IL-3. However, a decrease in cultured cell plating densit y resulted in ablation of this SCF-stimulation of CFU-Meg colonies. CF U-Meg colony stimulation by SCF was dose dependent, even under serum-f ree conditions. The effects of SCF in other in vitro and in vivo anima l model systems are reviewed.