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Proc Natl Acad Sci U S A. May 1989; 86(10): 3828–3832.
PMCID: PMC287234

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

Abstract

The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstitution. Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability. We examined greater than 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation. First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service. Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3. The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (less than 1.077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells. Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater. The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution.

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Selected References

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  • Broxmeyer HE. Colony assays of hematopoietic progenitor cells and correlations to clinical situations. Crit Rev Oncol Hematol. 1984;1(3):227–257. [PubMed]
  • Williams DE, Lu L, Broxmeyer HE. Characterization of hematopoietic stem and progenitor cells. Immunol Res. 1987;6(4):294–304. [PubMed]
  • To LB, Juttner CA. Peripheral blood stem cell autografting: a new therapeutic option for AML? Br J Haematol. 1987 Jul;66(3):285–288. [PubMed]
  • Kessinger A, Armitage JO, Landmark JD, Smith DM, Weisenburger DD. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. Blood. 1988 Mar;71(3):723–727. [PubMed]
  • Körbling M, Dörken B, Ho AD, Pezzutto A, Hunstein W, Fliedner TM. Autologous transplantation of blood-derived hemopoietic stem cells after myeloablative therapy in a patient with Burkitt's lymphoma. Blood. 1986 Feb;67(2):529–532. [PubMed]
  • Kessinger A, Armitage JO, Landmark JD, Weisenburger DD. Reconstitution of human hematopoietic function with autologous cryopreserved circulating stem cells. Exp Hematol. 1986 Mar;14(3):192–196. [PubMed]
  • Reiffers J, Bernard P, David B, Vezon G, Sarrat A, Marit G, Moulinier J, Broustet A. Successful autologous transplantation with peripheral blood hemopoietic cells in a patient with acute leukemia. Exp Hematol. 1986 May;14(4):312–315. [PubMed]
  • Bell AJ, Figes A, Oscier DG, Hamblin TJ. Peripheral blood stem cell autografting. Lancet. 1986 May 3;1(8488):1027–1027. [PubMed]
  • Tilly H, Bastit D, Lucet JC, Esperou H, Monconduit M, Piguet H. Haemopoietic reconstitution after autologous peripheral blood stem cell transplantation in acute leukaemia. Lancet. 1986 Jul 19;2(8499):154–155. [PubMed]
  • Castaigne S, Calvo F, Douay L, Thomas F, Benbunan M, Gerota J, Degos L. Successful haematopoietic reconstitution using autologous peripheral blood mononucleated cells in a patient with acute promyelocytic leukaemia. Br J Haematol. 1986 May;63(1):209–211. [PubMed]
  • Juttner CA, To LB, Haylock DN, Branford A, Kimber RJ. Circulating autologous stem cells collected in very early remission from acute non-lymphoblastic leukaemia produce prompt but incomplete haemopoietic reconstitution after high dose melphalan or supralethal chemoradiotherapy. Br J Haematol. 1985 Dec;61(4):739–745. [PubMed]
  • White DG, Woolf AD, Mortimer PP, Cohen BJ, Blake DR, Bacon PA. Human parvovirus arthropathy. Lancet. 1985 Feb 23;1(8426):419–421. [PubMed]
  • Abrams RA, Glaubiger D, Appelbaum FR, Deisseroth AB. Result of attempted hematopoietic reconstitution using isologous, peripheral blood mononuclear cells: a case report. Blood. 1980 Sep;56(3):516–520. [PubMed]
  • Hershko C, Gale RP, Ho WG, Cline MJ. Cure of aplastic anaemia in paroxysmal nocturnal haemoglobinuria by marrow transfusion from identical twin: Failure of peripheral-leucocyte transfusion to correct marrow aplasia. Lancet. 1979 May 5;1(8123):945–947. [PubMed]
  • Migliaccio G, Migliaccio AR, Petti S, Mavilio F, Russo G, Lazzaro D, Testa U, Marinucci M, Peschle C. Human embryonic hemopoiesis. Kinetics of progenitors and precursors underlying the yolk sac----liver transition. J Clin Invest. 1986 Jul;78(1):51–60. [PMC free article] [PubMed]
  • Prümmer O, Fliedner TM. The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution. Int J Cell Cloning. 1986 Jul;4(4):237–249. [PubMed]
  • Nakahata T, Ogawa M. Hemopoietic colony-forming cells in umbilical cord blood with extensive capability to generate mono- and multipotential hemopoietic progenitors. J Clin Invest. 1982 Dec;70(6):1324–1328. [PMC free article] [PubMed]
  • Leary AG, Ogawa M, Strauss LC, Civin CI. Single cell origin of multilineage colonies in culture. Evidence that differentiation of multipotent progenitors and restriction of proliferative potential of monopotent progenitors are stochastic processes. J Clin Invest. 1984 Dec;74(6):2193–2197. [PMC free article] [PubMed]
  • Smith S, Broxmeyer HE. The influence of oxygen tension on the long-term growth in vitro of haematopoietic progenitor cells from human cord blood. Br J Haematol. 1986 May;63(1):29–34. [PubMed]
  • Bodger MP. Isolation of hemopoietic progenitor cells from human umbilical cord blood. Exp Hematol. 1987 Sep;15(8):869–876. [PubMed]
  • Hassan MW, Lutton JD, Levere RD, Rieder RF, Cederqvist LL. In vitro culture of erythroid colonies from human fetal liver and umbilical cord blood. Br J Haematol. 1979 Apr;41(4):477–484. [PubMed]
  • Vainchenker W, Guichard J, Breton-Gorius J. Growth of human megakaryocyte colonies in culture from fetal, neonatal, and adult peripheral blood cells: ultrastructural analysis. Blood Cells. 1979 Mar 23;5(1):25–42. [PubMed]
  • Knudtzon S. In vitro growth of granulocytic colonies from circulating cells in human cord blood. Blood. 1974 Mar;43(3):357–361. [PubMed]
  • Salahuddin SZ, Markham PD, Ruscetti FW, Gallo RC. Long-term suspension cultures of human cord blood myeloid cells. Blood. 1981 Nov;58(5):931–938. [PubMed]
  • GENGOZIAN N, MAKINODAN T. Mortality of mice as affected by variation of the x-ray dose and number of nucleated rat bone marrow cells injected. Cancer Res. 1957 Nov;17(10):970–975. [PubMed]
  • Silobrcić V, Trentin JJ. On the mechanism of "homologous disease" in sublethally irradiated mice. Transplantation. 1966 Nov;4(6):719–731. [PubMed]
  • Allegretti N. Late mortality in midlethally irradiated mice given injections of hematopoietic cells from F-1 hybrids. J Natl Cancer Inst. 1968 Mar;40(3):431–440. [PubMed]
  • Ma DD, Varga DE, Biggs JC. Donor marrow progenitors (CFU-Mix, BFU-E and CFU-GM) and haemopoietic engraftment following HLA matched sibling bone marrow transplantation. Leuk Res. 1987;11(2):141–147. [PubMed]
  • Douay L, Gorin NC, Mary JY, Lemarie E, Lopez M, Najman A, Stachowiak J, Giarratana MC, Baillou C, Salmon C, et al. Recovery of CFU-GM from cryopreserved marrow and in vivo evaluation after autologous bone marrow transplantation are predictive of engraftment. Exp Hematol. 1986 Jun;14(5):358–365. [PubMed]
  • Faille A, Maraninchi D, Gluckman E, Devergie A, Balitrand N, Ketels F, Dresch C. Granulocyte progenitor compartments after allogeneic bone marrow grafts. Scand J Haematol. 1981 Mar;26(3):202–214. [PubMed]
  • Spitzer G, Verma DS, Fisher R, Zander A, Vellekoop L, Litam J, McCredie KB, Dicke KA. The myeloid progenitor cell--its value in predicting hematopoietic recovery after autologous bone marrow transplantation. Blood. 1980 Feb;55(2):317–323. [PubMed]
  • Broxmeyer HE, Lu L, Cooper S, Tushinski R, Mochizuki D, Rubin BY, Gillis S, Williams DE. Synergistic effects of purified recombinant human and murine B cell growth factor-1/IL-4 on colony formation in vitro by hematopoietic progenitor cells. Multiple actions. J Immunol. 1988 Dec 1;141(11):3852–3862. [PubMed]
  • Broxmeyer HE, Bognacki J, Ralph P, Dörner MH, Lu L, Castro-Malaspina H. Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro. Blood. 1982 Sep;60(3):595–607. [PubMed]
  • Lu L, Welte K, Gabrilove JL, Hangoc G, Bruno E, Hoffman R, Broxmeyer HE. Effects of recombinant human tumor necrosis factor alpha, recombinant human gamma-interferon, and prostaglandin E on colony formation of human hematopoietic progenitor cells stimulated by natural human pluripotent colony-stimulating factor, pluripoietin alpha, and recombinant erythropoietin in serum-free cultures. Cancer Res. 1986 Sep;46(9):4357–4361. [PubMed]
  • Jacobsen N, Broxmeyer HE, Grossbard E, Moore MA. Colony-forming units in diffusion chambers (CFU-d) and colony-forming units in agar culture (CFU-c) obtained from normal human bone marrow: a possible parent-progeny relationship. Cell Tissue Kinet. 1979 Mar;12(2):213–226. [PubMed]
  • Ferrero D, Broxmeyer HE, Pagliardi GL, Venuta S, Lange B, Pessano S, Rovera G. Antigenically distinct subpopulations of myeloid progenitor cells (CFU-GM) in human peripheral blood and marrow. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4114–4118. [PMC free article] [PubMed]
  • Lu L, Broxmeyer HE. Comparative influences of phytohemagglutinin-stimulated leukocyte conditioned medium, hemin, prostaglandin E, and low oxygen tension on colony formation by erythroid progenitor cells in normal human bone marrow. Exp Hematol. 1985 Nov;13(10):989–993. [PubMed]
  • English D, Lamberson R, Graves V, Akard LP, McCarthy LJ, Jansen J. Semiautomated processing of bone marrow grafts for transplantation. Transfusion. 1989 Jan;29(1):12–16. [PubMed]
  • Williams DE, Broxmeyer HE. Interleukin-1 alpha enhances the in vitro survival of purified murine granulocyte-macrophage progenitor cells in the absence of colony-stimulating factors. Blood. 1988 Nov;72(5):1608–1615. [PubMed]
  • Broxmeyer HE, Williams DE. The production of myeloid blood cells and their regulation during health and disease. Crit Rev Oncol Hematol. 1988;8(3):173–226. [PubMed]
  • Jones RJ, Sharkis SJ, Celano P, Colvin OM, Rowley SD, Sensenbrenner LL. Progenitor cell assays predict hematopoietic reconstitution after syngeneic transplantation in mice. Blood. 1987 Oct;70(4):1186–1192. [PubMed]
  • Rowley SD, Zuehlsdorf M, Braine HG, Colvin OM, Davis J, Jones RJ, Saral R, Sensenbrenner LL, Yeager A, Santos GW. CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged bone marrow. Blood. 1987 Jul;70(1):271–275. [PubMed]
  • Nakahata T, Ogawa M. Identification in culture of a class of hemopoietic colony-forming units with extensive capability to self-renew and generate multipotential hemopoietic colonies. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3843–3847. [PMC free article] [PubMed]
  • Williams DE, Boswell HS, Floyd AD, Broxmeyer HE. Pluripotential hematopoietic stem cells in post-5-fluorouracil murine bone marrow express the Thy-1 antigen. J Immunol. 1985 Aug;135(2):1004–1011. [PubMed]
  • Rowley SD, Sharkis SJ, Hattenburg C, Sensenbrenner LL. Culture from human bone marrow of blast progenitor cells with an extensive proliferative capacity. Blood. 1987 Mar;69(3):804–808. [PubMed]
  • Leary AG, Ogawa M. Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors. Blood. 1987 Mar;69(3):953–956. [PubMed]
  • Brandt J, Baird N, Lu L, Srour E, Hoffman R. Characterization of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro. J Clin Invest. 1988 Sep;82(3):1017–1027. [PMC free article] [PubMed]
  • To LB, Dyson PG, Branford AL, Haylock DN, Kimber RJ, Juttner CA. CFU-mix are no better than CFU-GM in predicting hemopoietic reconstitutive capacity of peripheral blood stem cells collected in the very early remission phase of acute nonlymphoblastic leukemia. Exp Hematol. 1987 May;15(4):351–354. [PubMed]

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