28 Large-Scale Ex Vivo Expansion of Human Megakaryocytes for Clinical Use

This chapter will describe a method used to produce human megakaryocytes in vitro (see Fig. 1 ), in high yield, for a clinical product to supplement progenitor cell transplants. Producing significant numbers of megakaryocytes from human progenitor cells requires specific combinations of cytokines to promote their proliferation and maturation in vitro. Thrombopoietin (TPO) is the primary regulator of megakaryocytopoiesis (1 -6 ). Other cytokines, including interleukin-3 (IL-3), IL-6, IL-11, stem cell factor (SCF; also known as kit- ligand), and granulocyte-macrophage colony stimulating factor (GM-CSF) are also capable of promoting megakaryocytopoiesis and will synergize with TPO to increase megakaryocyte proliferation (reviewed in ref. 7 ).