COMPARATIVE EFFECTS OF SUPPRESSIVE CYTOKINES ON ISOLATED SINGLE CD34(+++) STEM PROGENITOR CELLS FROM HUMAN BONE-MARROW AND UMBILICAL-CORD BLOOD PLATED WITH AND WITHOUT SERUM/

A number of cytokines have been implicated in the suppression of myelo id stem and progenitor cell proliferation It has been suggested that s ome of these act directly on the stem/progenitors themselves, based on the effects of these cells, plated in culture at low seeding densitie s, on highly enriched populations. These studies, however, do not defi nitively rule out effects on accessory cells. To more rigorously evalu ate direct-acting suppressive effects of cytokines, such cytokines wer e assessed for their effects on colony formation initiated by single b one marrow (BM) or umbilical cord blood (CB) CD34(+++) cells sorted in to single wells in the presence of a combination of growth-stimulating cytokines (erythropoietin [Epo], steel factor [SLF], granulocyte-macr ophage colony-stimulating factor [GM-CSF], and interleukin-3 [IL-3]) a nd in the presence or absence of serum. Under these conditions, it was demonstrated that H-ferritin, transforming growth factor-beta 1 (TGF- beta 1), and members of the chemokine family (macrophage inflammatory protein-1 alpha [MIP-1 alpha], MIP-2 beta, platelet factor 4 [PF4], IL -8, and macrophage chemotactic and activating factor [MCAF]) had direc t significant suppressive activities on single stem/progenitor cells f rom adult human BM in the presence or absence of serum. Single sorted CB cells were much less sensitive to inhibition by these cytokines. Th e reasons for this differential sensitivity are not known. Of possible relevance to this for cytokines, such as H-ferritin and the chemokine s that have actions during S-phase of the cell cycle, CB progenitors w ere in slower cycle at initiation of culture than were BM progenitors.