CONDITIONED MEDIUM FROM PRIMARY PORCINE ENDOTHELIAL-CELLS ALONE PROMOTES THE GROWTH OF PRIMITIVE HUMAN HEMATOPOIETIC PROGENITOR CELLS WITH A HIGH REPLATING POTENTIAL - EVIDENCE FOR A NOVEL EARLY HEMATOPOIETIC ACTIVITY

The authors have recently shown that direct contact with primary porci ne microvascular endothelial cell monolayers (PMVECs) in combination w ith haematopoietic growth factors enhances the expansion of primitive human haematopoietic CD34(+) bone marrow progenitor cells. It is now d emonstrated that serum-free conditioned medium (PMVEC CRI, concentrate d 70x for proteins >30kDa) from untreated PMVECs contains haematopoiet ic growth factor activity that enhances the in vitro proliferation, ha ematopoietic cell production, and colony cell formation of primitive h uman haematopoietic progenitor cells, In combination with exogeneously added human growth factors such as interleukin 3 (IL-3), granulocyte- macrophage colony-stimulating factor (GM-CSF) and EPO, PMVEC CM enhanc es the proliferation and colony growth of human haematopoietic CD34(+) cells, In contrast, PMVEC CM has no significant synergistic activity on either stem cell factor (SCF) or flt3-ligand-induced CD34(+) cell p roliferation, cell production or colony formation, Blocking mAbs again st the c-kit receptor have no effect on PMVEC CM-induced CD34(+) cell proliferation at titres that completely suppress SCF-induced prolifera tion, Moreover, it is shown that this haematopoietic growth factor sup ports the proliferation and colony formation of murine, non-human prim ate, and porcine marrow progenitor cells without any apparent species- specific restrictions in its activity, These finding suggest that PMVE C CRI contains a novel early haematopoietic activity. (C) 1997 Academi c Press Limited.