RECOMBINANT HUMAN MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR (RHUMGDF), A LIGAND FOR C-MPL, PRODUCES FUNCTIONAL HUMAN PLATELETS IN-VITRO

Platelet formation, occurring from bone marrow or lung megakaryocytes, has been difficult to study mechanistically. Recombinant human megaka ryocyte growth and development factor (rHuMGDF), a recently described cytokine, has now been used to establish an in vitro system in which t his important and little understood process occurs, CD34(+) cells cult ured with rHuMGDF develop into megakaryocytes which form long cytoplas mic extensions (proplatelets) that fragment into platelet-sized partic les (in vitro platelets). Morphologically, in vitro and human plasma-d erived platelets (control platelets) are virtually identical with resp ect to size, dense granule distribution and ultrastructural features. Functionally, in vitro and control platelets have similar aggregation and activation responses, and similarly incorporate mepacrine into den se granules, These findings suggest that rHuMGDF is sufficient to gene rate platelet-synthesizing megakaryocytes from CD34(+) cells and provi de an experimental setting in which the study of human platelet format ion can be adequately performed.