DEFECTION OF A PRIMITIVE MEGAKARYOCYTE PROGENITOR-CELL IN HUMAN FETALBONE-MARROW

Ontogeny-related changes in megakaryocyte (MK) progenitor cells were a nalyzed to further define the cellular hierarchy occurring during huma n MK development. CD34(+) cells were selected from human low-density a dult bone marrow (ABM) or unfractionated fetal bone marrow (FBM) and a ssayed for MK colony formation in a serum-depleted fibrin clot assay s ystem. At days 3, 7, 12, 16, 21, and 28 of incubation, MK colonies wer e analyzed for colony number, size, and number of foci of development. Unifocal CFU-MK-derived colonies cloned from FBM formed after fewer d ays of in vitro culture and were 2.6-fold larger than those colonies c loned from ABM. However, the frequency of CFU-MK-derived colonies clon ed from ABM was significantly greater. The MK colonies cloned from FBM morphologically consisted of both pure MK colonies and mixed MK-conta ining colonies, in which a core of CD41(-) cells were surrounded by CD 41(+) MKs. Large colonies resembling the primitive burst-forming unit- MK (BFU-MK) also were assayable from both FBM and ABM. These BFU-MK-de rived colonies appeared after fewer days of incubation when FBM was as sayed compared to ABM, but at a significantly lower frequency. In addi tion, large unifocal MK colonies consisting of >300 cells (300-1000) a ppeared from cells cloned from FBM but not ABM. This type of colony, w hich appears to represent a unique type of MK progenitor cell, was ter med a high proliferative potential cell-MK (HPPC-MK). Such colonies re present a relatively rare MK progenitor. We conclude that there are si gnificant ontologic changes in human MK progenitor cell development. T he kinetics of MK colony formation from ABM differs significantly from that of FBM. Furthermore, the proliferative capacity of fetal MK prog enitor cells appears to be far greater than that of ABM. In addition, a more primitive lineage-restricted MK progenitor cell with extensive proliferative capacity, the HPPC-MK, was assayable exclusively from FB M.