Stem Cells, Vol 12, 616-625, Copyright © 1994 by AlphaMed Press
Modulation of human cord blood progenitor cell growth by recombinant human interleukin 3 (IL-3), IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF) and stem cell factor (SCF) in serum- supplemented and serum-free medium
C De Bruyn, A Delforge, D Bron, P Ley, D de Hemptinne and P Stryckmans
Service de Medecine Interne et Laboratoire d'Investigation Clinique Henri Tagnon, Institut J. Bordet, Brussels, Belgium.
We evaluated the growth of cord blood myeloid progenitors or colony forming
units granulocyte-macrophage (CFU-GM) and their response to various
recombinant growth factors or colony stimulating factors (CSFs):
interleukin 3 (IL-3), IL-6, granulocyte-macrophage CSF (GM-CSF) and stem
cell factor (SCF). Using classical stimulant (human placenta conditioned
medium or HPCM), we observed a significantly higher day- 14/day-7 CFU-GM
ratio in CB than in bone marrow (BM). The association of IL-3, IL-6, GM-CSF
and SCF induced significantly more CB day-14 CFU- GM than HPCM. This effect
is significantly greater in CB than in bone marrow. Since fetal calf serum
(FCS) is known to contain inhibitors, we have compared the ability of CSFs
to induce CFU-GM formation in FCS- supplemented and FCS-free culture. In
CB, using HPCM, we obtained significantly more CFU-GM in FCS-free medium
than in FCS-supplemented medium. This difference was corrected by the
addition of anti- transforming growth factor-beta (TGF-beta) neutralizing
antibody. However, with the association of the four CSFs, no significant
difference between FCS and FCS-free culture was observed. In conclusion: a)
day-14/day-7 CFU-GM ratio was higher in CB than in BM indicating that CB
CFU-GM are more primitive than BM CFU-GM; b) FCS can be successfully
replaced by serum-free medium; c) FCS contains inhibitors of day-14 CFU-GM
and among them TGF-beta; and d) the association IL-3, SCF, GM-CSF and IL-6
seems able to totally overcome the inhibitory effect of FCS.
