POSSIBLE MECHANISMS ACCOUNTING FOR THE GROWTH-FACTOR INDEPENDENCE OF HEMATOPOIETIC PROGENITORS FROM UMBILICAL-CORD BLOOD

Hematopoietic progenitors obtained from the bone marrow of healthy adu lts fail to undergo clonogenic maturation in vitro if a source of hema topoietic growth factors is not included in the culture dishes. In con trast, a fraction of similarly purified progenitors obtained from umbi lical cord blood undergo clonogenic maturation even in the absence of added growth factors. We postulated that production of hematopoietic g rowth factors within the culture dishes containing the progenitors of umbilical cord blood origin might be responsible. We postulated furthe r, that this production might be by non-progenitor cells co-plated alo ng with the progenitors, or alternatively by CD34(+) cells themselves, or by cells clonally derived from CD34(+) cells. To test these possib ilities we first assessed the effect of including in the cultures neut ralizing antibody directed against various growth factors. Inclusion o f anti-granulocyte macrophage colony-stimulating factor (GM-CSF) and a nti-interleukin-3 (IL-3) (but not anti-IL-2) significantly reduced the growth factor independence of cord blood progenitors (P < .005 and P < .01). Inclusion of both anti-GM-CSF and anti-IL-3 almost completely ablated the spontaneous colony growth (P < .001). Inclusion of IL-10 a lso reduced, in a concentration-dependent fashion, the spontaneous gen eration of umbilical cord blood-derived colonies. Transcripts for GM-C SF and IL-3 were detected, by reverse transcriptase-polymerase chain r eaction (RT-PCR), in the CD34(+) cells from cord blood and from adult marrow. When plated without added growth factors, however, the CD34(+) cells of adult marrow origin failed to produce colonies, whereas 6% o f cord blood CD34(+) cells similarly cultured did so. When these growt h factor independent colonies were plucked from culture, transcripts f or GM-CSF and IL-3 were identified in all. We conclude that production of GM-CSF and IL-3 occurs within culture dishes containing hematopoie tic progenitors of umbilical cord origin, and that this explains some of their apparently unique features of in vitro growth. (C) 1994 by Th e American Society of Hematology.