Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow.
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 10(6) 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 +/- 0.6/10(6) nucleated cells (69.6 +/- 10/microL 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, alpha-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 +/- 2.0/10(6) nucleated cells) and bone marrow (12.6 +/- 3.6/10(6) 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.
Campagnoli
C
C
Department of Maternal and Fetal Medicine, Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, London, United Kingdom. c.campagnoli@ic.ac.uk
Roberts
I A
IA
Kumar
S
S
Bennett
P R
PR
Bellantuono
I
I
Fisk
N M
NM
D000273:Adipose Tissue / Q000166:cytology / Q000196:embryology; D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology*; D002455:Cell Division; D002469:Cell Separation; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D008099:Liver / Q000166:cytology / Q000196:embryology; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D010012:Osteogenesis / Q000276:immunology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D012867:Skin / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D006684:HLA-DR Antigens