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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, 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 ± 2.0/106 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.

© 2001 by The American Society of Hematology.
 

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