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Factors modulating circulation of hematopoietic progenitor cells in cord blood and neonates

      Background

      Hematopoietic progenitor cells (HPC) circulate at high levels at birth and disappear rapidly afterwards, but the underlying mechanism it is not known. The aim of this study was to assess circulating HPC in cord blood at different gestational ages and shortly after birth and concomitantly study the biologic markers involved in this phenomenon.

      Methods

      All samples were analyzed for CD34+ cells, colony-forming units (CFU) and cytokines.

      Results

      The results obtained confirmed a slight decrease in HPC concentration during the late stage of fetal life (R2 = 0.41). After birth, CD34+ cells showed a rapid decline from circulation: 25 ± 29% at 3 h, 51 ± 42% at 12 h and 80 ± 48% at 60 h. CFU cleared following a similar pattern. Cord plasma showed higher concentrations of stem cell factor (SCF), fetal liver tyrosine kinase 3-ligand (FLT3l), erythrpoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and interleukin-11 (IL-11) compared with an adult control. Interestingly, the EPO concentration in newborn plasma correlated with the kinetics of HPC decline after birth. Moreover, we observed an up-regulation of l-selectin and a down-regulation of CXCR4 expression in CD34+ cells 3 h after birth.

      Discussion

      These data combined suggest that an active homing process results in the clearance of HPC from the circulation immediately after birth.

      Keywords

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      References

        • Tavian M.
        • Péault B.
        The changing cellular environments of hematopoiesis in human development in utero.
        Exp Hematol. 2005; 33: 1062-1069
        • Broxmeyer H.E.
        • Douglas G.W.
        • Hangoc G.
        • et al.
        Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.
        Proc Natl Acad Sci USA. 1989; 86: 3828-3832
        • Migliaccio G.
        • Baiocchi M.
        • Hamel N.
        • et al.
        Circulating progenitor cells in human ontogenesis: response to growth factors and replating potential.
        J Hematother. 1996; 5: 161-170
        • Geissler K.
        • Geissler W.
        • Hinterberger W.
        • et al.
        Circulating committed and pluripotent haemopoietic progenitor cells, in infants.
        Acta Haematol. 1986; 75: 18-22
        • Bizzarro M.J.
        • Bhandari V.
        • Krause D.S.
        • et al.
        Circulating stem cells in extremely preterm neonates.
        Acta Paediatr. 2007; 96: 521-525
        • Filshie R.J.
        Cytokines in haemopoietic progenitor mobilisation for peripheral blood stem cell transplantation.
        Curr Pharm Des. 2002; 8: 379-394
        • Zohren F.
        • Toutzaris D.
        • Klärner V.
        • et al.
        The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans.
        Blood. 2008; 111: 3893-3895
        • Juarez J.
        • Dela Pena A.
        • Baraz R.
        • et al.
        CXCR4 antagonists mobilize childhood acute lymphoblastic leukemia cells into the peripheral blood and inhibit engraftment.
        Leukemia. 2007; 21: 1249-1257
        • Peled A.
        • Petit I.
        • Kollet O.
        • et al.
        Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4.
        Science. 1999; 283: 845-848
        • Pratt G.
        • Rawstron A.C.
        • English A.E.
        • et al.
        Analysis of CD34+ cell subsets in stem cell harvests can more reliably predict rapidity and durability of engraftment than total CD34+ cell dose, but steady state levels do not correlate with bone marrow reserve.
        Br J Haematol. 2001; 114: 937-943
        • Dercksen M.W.
        • Gerritsen W.R.
        • Rodenhuis S.
        • et al.
        Expression of adhesion molecules on CD34+ cells: CD34+ L-selectin+ cells predict a rapid platelet recovery after peripheral blood stem cell transplantation.
        Blood. 1995; 85: 3313-3319
        • Li K.
        • Liu J.
        • Fok T.F.
        • et al.
        Human neonatal blood: stem cell content, kinetics of CD34+ cell decline and ex vivo expansion capacity.
        Br J Haematol. 1999; 104: 178-185
        • Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: a public health perspective
        Morb Mortal Wkly Rep. 1996; 45: 1-23
        • Broxmeyer H.E.
        • Hangoc G.
        • Cooper S.
        • et al.
        Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults.
        Proc Natl Acad Sci USA. 1992; 89: 4109-4113
        • Peault B.
        • Tavian M.
        Hematopoietic stem cell emergence in the human embryo and fetus.
        Ann NY Acad Sci. 2003; 996: 132-140
        • Ural S.H.
        • Sammel M.D.
        • Blakemore K.J.
        Determination of engraftment potential of human cord blood stem-progenitor cells as a function of donor cell dosage and gestational age in the NOD/SCID mouse model.
        Am J Obstet Gynecol. 2005; 193: 990-994
        • Kim J.P.
        • Lee Y.H.
        • Lee Y.A.
        • Kim Y.D.
        A comparison of the kinetics of nucleated cells and CD34+ cells in neonatal peripheral blood and cord blood.
        Biol Blood Marrow Transplant. 2007; 13: 478-485
        • Lim F.T.
        • Scherjon S.A.
        • van Beckhoven J.M.
        • et al.
        Association of stress during delivery with increased numbers of nucleated cells and hematopoietic progenitor cells in umbilical cord blood.
        Am J Obstet Gynecol. 2000; 183: 1144-1152
        • Cairo M.S.
        • Wagner E.L.
        • Fraser J.
        • et al.
        Characterization of banked umbilical cord blood hematopoietic progenitor cells and lymphocyte subsets and correlation with ethnicity, birth weight, sex, and type of delivery: a Cord Blood Transplantation (COBLT) Study report.
        Transfusion. 2005; 45: 856-866
        • Gekas C.
        • Dieterlen-Lièvre F.
        • Orkin S.H.
        • Mikkola H.K.
        The placenta is a niche for hematopoietic stem cells.
        Dev Cell. 2005; 8: 365-375
        • Zhang Y.
        • Li C.
        • Jiang X.
        • et al.
        Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells.
        Exp Hematol. 2004; 32: 657-664
        • Kamlin C.O.
        • O'Donnell C.P.
        • Davis P.G.
        • Morley C.J.
        Oxygen saturation in healthy infants immediately after birth.
        J Pediatr. 2006; 148: 585-589
        • Stevens C.E.
        • Gladstone J.
        • Taylor P.E.
        • et al.
        Placental/umbilical cord blood for unrelated-donor bone marrow reconstitution: relevance of nucleated red blood cells.
        Blood. 2002; 100: 2662-2664
        • Ervasti M.
        • Sankilampi U.
        • Heinonen S.
        • Punnonen K.
        Novel red cell indices indicating reduced availability of iron are associated with high erythropoietin concentration and low pH level in the venous cord blood of newborns.
        Pediatr Res. 2008; 64: 135-140
        • Calhoun D.A.
        • Christensen R.D.
        A randomized pilot trial of administration of granulocyte colony-stimulating factor to women before preterm delivery.
        Am J Obstet Gynecol. 1998; 179: 766-771
        • Mancinelli F.
        • Tamburini A.
        • Spagnoli A.
        • et al.
        Optimizing umbilical cord blood collection: impact of obstetric factors versus quality of cord blood units.
        Transplant Proc. 2006; 38: 1174-1176
        • Bertolini F.
        • Lazzari L.
        • Lauri E.
        • et al.
        Cord blood plasma-mediated ex vivo expansion of hematopoietic progenitor cells.
        Bone Marrow Transplant. 1994; 14: 347-353
        • Koenig J.M.
        • Baron S.
        • Luo D.
        • Benson N.A.
        • Deisseroth A.B.
        L-selectin expression enhances clonogenesis of CD34+ cord blood progenitors.
        Pediatr Res. 1999; 45: 867-870
        • Priestley G.V.
        • Scott L.M.
        • Ulyanova T.
        • Papayannopoulou T.
        Lack of alpha4 integrin expression in stem cells restricts competitive function and self-renewal activity.
        Blood. 2006; 107: 2959-2967
        • Broxmeyer H.E.
        Chemokines in hematopoiesis.
        Curr Opin Hematol. 2008; 15: 49-58
        • Forde S.
        • Tye B.J.
        • Newey S.E.
        • et al.
        Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells.
        Blood. 2007; 109: 1825-1833