Presence and characteristics of circulating megakaryocyte progenitor cells in human fetal blood

The in vitro growth of early (burst-forming unit-megakaryocyte [BFU- meg]) and late (colony-forming unit-megakaryocyte [CFU-meg]) megakaryocyte progenitors was investigated in midtrimester human fetal blood and compared with adult bone marrow. Most of the experiments were performed in a serum-free fibrin-clot assay, using purified hematopoietic progenitor (CD34+) cells. High BFU-meg and CFU-meg levels were found in human fetal blood, with a clear prevalence of BFU-meg (BFU-meg:CFU-meg ratio, 2.5:1), at variance with adult bone marrow, in which mature CFU-meg predominate (BFU-meg:CFU-meg ratio, 0.6:1). Fetal and adult megakaryocyte progenitors had a similar phenotypic profile for the expression of CD34, HLA-DR, and glycoprotein-complex IIB-IIIA. However, fetal BFU-meg were larger in size (number of megakaryocytic elements per colony) than adult BFU-meg, but were usually composed by only one or two foci of development. On the other hand, fetal and adult CFU-meg were similar in both morphology and size. Fetal megakaryocyte progenitors appeared earlier in culture and had an increased proliferative activity as demonstrated by the higher number of megakaryocyte progenitors in S phase with respect to adult CFU-meg and BFU-meg. Finally, fetal megakaryocyte progenitors displayed a higher sensitivity to stimulatory cytokines, in particular recombinant interleukin-3, than adult megakaryocyte progenitors, whereas they were inhibited by purified transforming growth factor-beta 1 in a similar fashion to adult megakaryocyte progenitors.