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Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 1967-1972
Circulating hematopoietic progenitor cells in first trimester
fetal blood
Cesare Campagnoli,
Nicholas Fisk,
Timothy Overton,
Phillip Bennett,
Timothy Watts, and
Irene Roberts
From the Department of Maternal and Fetal Medicine and the
Department of Haematology, Imperial College School of Medicine,
Hammersmith and Queen Charlotte's Hospitals, London, England.
The yolk sac and aorto-gonad-mesonephros region are well
recognized as the principal sites of hematopoiesis in the
developing embryo, and the liver is the principal site of
hematopoiesis in the fetus. However, little is known about
circulating hematopoietic stem and progenitor cells in early fetal
life. We investigated the number and characteristics of
circulating progenitors in first trimester blood of 64 human
fetuses (median gestational age, 10+4 weeks; range,
7+6-13+6 weeks). CD34+ cells accounted
for 5.1 ± 1.0% of CD45+ cells in first trimester blood, which is
significantly more than in term cord blood (0.4 ± 0.03%;
P = .0015). However, the concentration of CD34+ cells
(6.6 ± 2.4 × 104/mL) was similar to that in term
cord blood (5.6 ± 3.9 × 104/mL). The total number
of progenitors cultured from unsorted mononuclear cells (MNCs) in first
trimester blood was 19.2 ± 2.1 × 103/mL, which is
similar to that in term cord blood
(26.4 ± 5.6 × 103/mL). All lineages were
seen: colony-forming unit-GEMM (CFU-GEMM), CFU-GM, BFU-e,
BFU-MK, and CFU-MK. Clonogenic assays of CD34+ cells purified from
first trimester samples produced mainly two lineages: BFU-e
(39.0 ± 9.6 × 103/mL CD34+ cells) and CFU-GEMM
(22.6 ± 4.7 × 103/mL CD34+ cells). Short-term
liquid culture of first trimester blood MNCs in
SCF + IL-3 + Flt-3 (stem cell
factor + interleukin-3 + Flt-3) increased, by 7-fold, the
numbers of CFU-GEMM and induced a dramatic increase in BFU-e
(65.6 ± 12.1-fold). These data show that significant numbers of
committed and multipotent progenitors with capacity for expansion
circulate in first trimester fetal blood and can be CD34 selected.
These cells should be suitable targets for gene transfer and stem cell
transplantation and, because fetal hematopoietic progenitors have been
demonstrated in the maternal circulation from early gestation, may also
be manipulated for noninvasive prenatal diagnosis of major genetic disorders.
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