Phenotype and progeny of primitive adherent human hematopoietic progenitors

Hematopoietic progenitor cells can be classified as plastic- and stroma-adherent (P+S+), stroma-adherent (P-S+) and non-adherent (P-S-). Both P+S+ and P-S+ populations are detected in delta (delta) culture systems where they produce non-adherent (P-S-) granulocyte-macrophage colony-forming cells (CFU-GM) and erythroid burst-forming units (BFU-E). Here we demonstrate that the plastic-adherent progenitor cells (P delta cells) comprise 5-10 percent of the CD34+, population in adult human marrow. Moreover, they do not express CD3 or CD22 and 88 percent of them are CD38-, 88 percent are CD33- and 74 percent are HLA-DR-. Production of CFU-GM by purified plastic-adherent CD34+, adherent cells was 60 percent of the number produced by recombined CD34+, and CD34- fractions. We have shown also that the plastic-adherent P+S+ cells are the precursors of the stroma-adherent P-S+ cells (S delta cells), day 21 cobblestone-area forming cells (CAFC) and cells capable of sustained hematopoiesis in a modified long-term bone marrow culture system. These observations support the primitive nature of P delta cells and establish a phenotypic sequence of plastic and stroma adherence through stroma adherence to non-adherence in hematopoietic cell development. To further investigate the relationship between P delta cells, S delta cells and long-term culture-initiating cells (LTCIC), we cultured whole mononuclear cell tractions and plastic-adherent cell-depleted mononuclear cell fractions in long-term culture and in the S delta assay. The results indicated the P delta cells were inhibited in the presence of stromal cells.