Immunophenotypic characterization of human fetal liver hematopoietic stem cells during the midtrimester of gestation


      Objective: Our purpose was to define the extent to which gestational age influences the number of fetal liver cells that coexpress phenotypic markers associated with hematopoietic stem cells and major histocompatibility antigens. Study design: Fetal liver cells from abortuses of 9 to 24 weeks of gestation were studied (n = 61). Low-density nucleated liver cells were isolated on a discontinuous density gradient and subsequently incubated with antibodies that recognize markers of hematopoietic stem cells (i.e., CD33, CD34, CDw90, CD117, and CD123). Human leukocyte antigen class I (A, B, C) and class II (DR) antigens were also determined on these cells. Each sample was analyzed by immunocytochemistry and flow cytometry. Analysis of variance was used for statistical analysis. Results: Of the markers measured, only the percentage of CD123-positive cells increased significantly with gestational age (p < 0.01). The percentage of triple-positive cells (CD34+, CD117+, and CD123+) increased with age but did not reach significance (p = 0.05). Human leukocyte A, B, and C antigens were expressed on all nucleated cells from 9 to 24 weeks of gestation. Human leukocyte DR antigen, however, was expressed only on 50% of these cells. The percentage of cells that expressed both hematopoietic stem cell markers and DR antigen did not vary with gestational age. Conclusions: From 9 to 24 weeks of gestation the number of human fetal liver hematopoietic stem cells that coexpress major histocompatibility antigens increases with advancing gestational age, largely because the percentage of these cells remains constant while the liver mass increases.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Muench MO
        • Cupp J
        • Polakoff J
        • Roncarolo MG.
        Expression of CD33, CD38, and HLA-DR on CD34+ human fetal liver progenitors with a high proliferative potential.
        Blood. 1994; 83: 3170-3179
        • Plum J
        • DeSmedt M
        • Defresne M
        • Leclercq G
        • Vanderkerckhove B.
        Human CD34+ fetal liver stem cells in a mouse thymic microenvironment.
        Blood. 1994; 84: 1587-1593
        • Zanjani EC
        • Mackintosh FR
        • Harrison MR.
        Hematopoietic chimerism in sheep and non-human primates by in utero transplantation of fetal hematopoietic stem cells.
        Blood Cells. 1991; 17: 349-363
        • Tourraine J.
        In utero transplantation of fetal liver stem cells in humans.
        Blood Cells. 1991; 17: 379-387
        • Diukman R
        • Golbus MS.
        In utero stem cell therapy.
        J Reprod Med. 1992; 37: 515-520
        • Andrews RG
        • Singer J
        • Bersnstein ID.
        Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors.
        Blood. 1986; 67: 842-845
        • Berenson RJ
        • Andrews RG
        • Bensinger WI
        • Kalamasz D
        • Knitter G
        • Buckner CD
        • et al.
        CD34+ marrow cells engraft lethally irradiated baboons.
        J Clin Invest. 1988; 81: 951-955
        • Brandt J
        • Bridell RA
        • Stout EF
        • Leemhuis TB
        • Hoffman R.
        Role of c-kit ligand in the expansion of human hematopoietic progenitor cells.
        Blood. 1992; 79: 634-641
        • Papayannopoulou T
        • Brice M
        • Broudy VC
        • Zsebo KM.
        Isolation of c-kit receptor-expressing cells from bone marrow, peripheral blood, and fetal liver: functional properties and composite antigenic profile.
        Blood. 1991; 78: 1403-1412
        • Flake AW
        • Roncarolo M
        • Puck JM
        • Almeida-Porada G
        • Evans MI
        • Johnson MP
        • et al.
        Treatment of X-linked severe combined immunodeficiency by in utero transplantation of paternal bone marrow.
        N Engl J Med. 1996; 335: 1806-1810
        • Lansdorp PM
        • Dragowska W
        • Mayani H.
        Ontogeny-related changes in proliferative potential of human hematopoietic cells.
        J Exp Med. 1993; 178: 787-791
        • Rice HE
        • Hedrick MH
        • Flake AW
        • Donegan E
        • Harrison MR.
        Bacterial and fungal contamination of human fetal liver collected transvaginally for hematopoietic stem cell transplantation.
        Fetal Diagn Ther. 1993; 8: 74-78
        • Vaziri H
        • Dragowska W
        • Allsopp RC
        • Thomas TE
        • Hadey CB
        • Lansdorp PM.
        Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
        Proc Natl Acad Sci U S A. 1994; 91: 9857-9860
        • Zanjani ED
        • Flake AW
        • Rice H
        • Hedrick M
        • Tavassoli M.
        Long-term repopulating ability of xenogeneic transplanted human fetal liver hematopoietic stem cells in sheep.
        J Clin Invest. 1994; 93: 1051-1055
        • Abe J.
        Immunocytochemical characterization of lymphocyte development in human embryonic and fetal livers.
        Clin Immunol Immunopathol. 1989; 51: 13-21
        • Zanjani ED
        • Ascensao JL
        • Tavassoli M.
        Liver-derived fetal hematopoietic stem cells selectively and preferentially home to the fetal bone marrow.
        Blood. 1993; 81: 399-404
        • Westgren M
        • Ek S
        • Bui T
        • Hagenfeldt L
        • Markling L
        • Pschera H
        • et al.
        Establishment of a tissue bank for fetal stem cell transplantation.
        Acta Obstet Gynecol Scand. 1994; 73: 385-388
        • Brandt JE
        • Bhalla K
        • Hoffman R
        Effects of interleukin-3 and c-kit ligand on the survival of various classes of human hematopoietic progenitor cells.
        Blood. 1994; 83: 1507-1514
        • DiGiusto D
        • Chen S
        • Combs J
        • Webb S
        • Namikawa R
        • Tsukamoto A
        • et al.
        Human fetal bone marrow early progenitors for T, B, and myeloid cells are found exclusively in the population expressing high levels of CD34.
        Blood. 1994; 84: 421-432
        • Sonoda Y
        • Sakabe H
        • Ohmisono Y
        • Tanimukai S
        • Yokota S
        • Nakagawa S
        • et al.
        Synergistic action of stem cell factor and other burst-formation activities on proliferation of CD34+ highly purified blood progenitors expressing HLA-DR or different levels of c-kit protein.
        Blood. 1994; 84: 4099-4106
        • Ratajczak MZ
        • Luger SM
        • Dedel K
        • Abrehm J
        • Calabretta B
        • Gewirtz AM.
        Role of the kit protooncogene in normal and malignant human hematopoiesis.
        Proc Natl Acad Sci U S A. 1992; 89: 1710-1714
        • Tatake RJ
        • Zeff RA.
        Regulated expression of the major histocompatibility complex class I genes.
        Proc Soc Exp Biol Med. 1993; 203: 405-417
        • Daar A
        • Fuggle S
        • Fabre J
        • Ting A
        • Morris P.
        The detailed distribution of HLA-A,B,C antigens in normal human organs.
        Transplantation. 1984; 38: 287-292
        • Takahashi H.
        Antigen processing and presentation.
        Microbiol Immunol. 1993; 37: 1-9
        • Thoma SJ
        • Lamping CP
        • Ziegler BL.
        Phenotype analysis of hematopoietic CD34+ cell populations derived from human umbilical cord blood using flow cytometry and cDNA-polymerase chain reaction.
        Blood. 1994; 83: 2103-2114