Human megakaryocytopoiesis: in vitro regulation and characterization of megakaryocytic precursor cells by differentiation markers.

ABSTRACT

Understanding of human megakaryopoiesis has been improved by in vitro culture techniques, characterization of platelet proteins as differentiation markers and megakaryocyte purification. A continuum of megakaryocytic cells ranging from the CFU-MK (cell capable of proliferation) to the platelet has been demonstrated. CFU-MK is a heterogeneous population of cells which do not express platelet proteins other than platelet GP IIb and IIIa which may be present in low concentration. The main platelet proteins are synthesized later during differentiation of a 2N cell, just before the polyploidization process. Several homogeneous growth factors GM-CSF, interleukin 3 and erythropoietin are able to sustain human megakaryocyte colony formation. However, no specific MK-CSF has yet been purified. Purification of factors active on late stages of differentiation has proved difficult when using in vivo techniques to test their activity. However, recently such a factor has been purified to homogeneity by testing its action on the biosynthesis of PF4 by megakaryocytes. A negative regulation of megakaryopoiesis has been suggested by the inhibition of MK-colony formation by platelet products especially TGF-beta. A better understanding of human megakaryopoiesis may be of importance as it may allow modifications of platelet production in a clinical setting.