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Blood, 15 October 2001, Vol. 98, No. 8, pp. 2396-2402
HEMATOPOIESIS
Identification of mesenchymal stem/progenitor cells in
human first-trimester fetal blood, liver, and bone marrow
Cesare Campagnoli,
Irene A. G. Roberts,
Sailesh Kumar,
Phillip R. Bennett,
Ilaria Bellantuono, and
Nicholas M. Fisk
From the Department of Maternal and Fetal Medicine,
Institute of Reproductive and Developmental Biology; and the
Departments of Haematology and Immunology, Imperial College School of
Medicine, London, United Kingdom.
Human mesenchymal stem/progenitor cells (MSCs) have been identified
in adult bone marrow, but little is known about their presence during
fetal life. MSCs were isolated and characterized in first-trimester
fetal blood, liver, and bone marrow. When 106 fetal blood
nucleated cells (median gestational age, 10+2 weeks
[10 weeks, 2 days]) were cultured in 10% fetal bovine serum, the
mean number (± SEM) of adherent fibroblastlike colonies was 8.2 ± 0.6/106 nucleated cells (69.6 ± 10/µL fetal
blood). Frequency declined with advancing gestation. Fetal blood MSCs
could be expanded for at least 20 passages with a mean cumulative
population doubling of 50.3 ± 4.5. In their undifferentiated state,
fetal blood MSCs were CD29+, CD44+,
SH2+, SH3+, and SH4+; produced
prolyl-4-hydroxylase, -smooth muscle actin, fibronectin, laminin,
and vimentin; and were CD45 , CD34 ,
CD14 , CD68 , vWF , and
HLA-DR . Fetal blood MSCs cultured in adipogenic,
osteogenic, or chondrogenic media differentiated, respectively, into
adipocytes, osteocytes, and chondrocytes. Fetal blood MSCs supported
the proliferation and differentiation of cord blood CD34+
cells in long-term culture. MSCs were also detected in first-trimester fetal liver (11.3 ± 2.0/106 nucleated cells) and bone
marrow (12.6 ± 3.6/106 nucleated cells). Their
morphology, growth kinetics, and immunophenotype were comparable to
those of fetal blood-derived MSCs and similarly differentiated along
adipogenic, osteogenic, and chondrogenic lineages, even after sorting
and expansion of a single mesenchymal cell. MSCs similar to those
derived from adult bone marrow, fetal liver, and fetal bone marrow
circulate in first-trimester human blood and may provide novel targets
for in utero cellular and gene therapy.

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