Human megakaryocyte progenitor cells

Megakaryocytopoiesis is a complex biological process involving a series of cellular events that is initiated with the pluripotent hematopoietic stem cell and eventually results in the biogenesis of platelets shed by mature megakaryocytes (MK). A hierarchy of human MK progenitor cells has been defined by means of studies of in vitro megakaryocytopoiesis. A number of in vitro clonal assays have been established that have aided in the characterization of each of these MK progenitor cells which can be distinguished by their cellular phenotype, physical characteristics, chemosensitivity, kinetics of colony formation, the size of the colonies that each progenitor cell subclass is capable of producing, and the cytokines required to induce such progenitor-cell-derived colony formation. The kinetics of appearance of these various classes of MK colonies derived from MK progenitor cells of differing proliferative capacity are consistent with a sequential developmental relationship between these various cellular subpopulations. The most primitive lineage-restricted MK progenitor cell identified to date is termed the high proliferative potential cell-MK (HPPC-MK). The HPPC-MK can be assayed from fetal but not adult human marrow, and in vitro it forms large unifocal pure MK colonies consisting of more than 300 cells (300 to 1,000). The burst forming unit-megakaryocyte is the most primitive MK progenitor cell that can be assayed from a variety of adult hematopoietic tissues, while the colony forming unit-megakaryocyte is the most differentiated MK progenitor cell still capable of forming pure MK colonies in vitro. Furthermore, a number of multipotent progenitor cells have been identified that are capable of producing colonies composed of multiple hematopoietic lineages of which MKs represent a minority component. A bipotent erythromegakaryocytic progenitor cell in human marrow has been carefully characterized that has the unique ability to form colonies composed exclusively of MKs and erythroblasts. This bipotent progenitor cell has been termed the burst-forming unit erythroid/MK and is indicative of the close linkage between features of the erythroid and megakaryocytic lineages. Recently the ex vivo incubation of CD34+ cells in the presence of a combination of cytokines has resulted in the generation of cell populations enriched for MKs and MK progenitor cells. Such an ex vivo generated product may serve as a source of a new generation of transfusion products capable of supporting thrombocytopenic patients.