Fetal liver generates low CD4 hematopoietic cells in murine stromal
cultures
A Tocci, F Rezzoug, K Wahbi and JL Touraine
Transplantation and Clinical Immunology Unit, INSERM U 80, Lyon, France.
We have demonstrated that 0.2% to 11% of cells from the fetal liver (FL)
reacted specifically with high concentrations of anti-CD4 monoclonal
antibody (MoAb). CD4+ cells from FL were similar in surface phenotype and
fluorescence characteristics to the CD4+ population found previously in
adult bone marrow (BM). FL and BM cells were seeded in cultures that allow
differentiation to primitive precursors. FL cells released many low CD4+
and low Thy+ cells in the supernatant, while BM cells seeded under the same
conditions did not. We studied the nonadherent cells harvested from 10-day
FL cultures (greater than 90% low CD4+). In methylcellulose, they were able
to produce more colonies that appear to be characteristic of earlier stages
in the hierarchy of hematopoietic precursors (especially erythroid bursts
and colonies composed of both myeloid and erythroid elements) in comparison
with CD4- cells from 10-day BM cultures. CD4+ cells harvested from FL
cultures initiated secondary cultures containing both a stromal layer and
large hematopoietic colonies when replated under conditions similar to
those of primary cultures. Furthermore, a limited number of CD4+ cells from
10-day FL cultures were able to repopulate lethally irradiated mice.
Although we cannot formally exclude the possibility that the low CD4 cells
produced in FL cultures were derived exclusively from the proliferation of
the few CD4 cells found in fresh FL, the dynamic analysis of the
development of these cells in culture favors the generation of this
important population from a CD4- subset of hematopoietic stem cells (HSCs).
We speculate that FL contains a prevalent population of very primitive
cells not expressing the CD4 antigen, tentatively called "pre-low CD4
precursors." These primitive cells can differentiate into low CD4+ cells
that share many characteristics with pluripotent HSCs of the adult type.
These data indicate the possibility of using hematopoietic progenitors
obtained by the expansion/differentiation of fetal stem cells in culture
for transplantation purposes.
Volume 85,
Issue 6,
pp. 1463-1471,
03/15/1995
Copyright © 1995 by The American Society of Hematology
