Skip to main content
Log in

What is the future for cord blood stem cells?

  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Stem and progenitor cells are present in cord blood at a high frequency making these cells a major target population for experimental and clinical studies. Over the past decade there has been considerable developments in cord blood research and transplantation but despite the rapid progress many problems remain. The initial hope that cord blood would be an alternative source of haemopoietic cells for transplantation has been tempered by the fact that there are insufficient cells in most cord blood collections to engraft an adult of average weight. In attempts to increase the cell number, a plethora of techniques for ex-vivo expansion have been developed.These techniques have also proved useful for gene therapy. As cord blood cells possess unique properties this allows them to be utilised as suitable vehicles for gene therapy and long-term engraftment of transduced cells has been achieved. Current work examining the nature of the stem cells present in this haematological source indicates that cord blood contains not only haemopoietic stem cells but also primitive non-haemopoietic cells with high proliferative and developmental potential. As attention focuses on stem cell biology and the controversies surrounding the potential use of embryonic stem cells in treatment of disease, the properties of stem cells from other sources including cord blood are being re-appraised. The purpose of this article is to review some of the current areas of work and highlight biological problems associated with the use of cord blood cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abonour R, Williams DA, Einhorn L, Hall KM, Chen J, Coffman J, Traycoff CM, Bank A, Kato I, Ward M, Williams SD, Hromas R, Robertson MJ, Smith FO, Woo D, Mills B, Srour EF & Cornetta K (2000) Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells. Nat Med 6: 652–658.

    Article  PubMed  CAS  Google Scholar 

  • Barquinero J, Segovia, JC, Ramírez M, Limón A, Güenechea G, Puig T, Briones J, García J & Bueren JA (2000) Efficient transduction of human hematopoietic repopulating cells generating stable engraftment of transgene-expressing cells in NOD/SCID mice. Blood 95: 3085–3093.

    PubMed  CAS  Google Scholar 

  • Bertolini F, Battaglia M, Pedrazzoli P, Da Prada GA, Lanza A, Soligo D, Caneva L, Sarina B, Murphy S, Thomas T & della Cuna GR (1997) Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients. Blood 89: 2679–2688.

    PubMed  CAS  Google Scholar 

  • Borras FE, Matthews NC, Patel R & Navarette C (2000) Dendritic cells can be successfully generated from CD34+ cord blood cells in the presence of autologous cord blood plasma. Bone Marrow Transplant 26: 371–376.

    Article  PubMed  CAS  Google Scholar 

  • Briddell RA, Kern BP, Zilm KL, Stoney GB & McNiece IK (1997) Purification of CD34+ cells is essential for optimal ex vivo expansion of umbilical cord blood cells. J Hematother 6: 145–150.

    PubMed  CAS  Google Scholar 

  • Condiotti R, Zakai YB, Barak V & Nagler A (2001) Ex vivo expansion of CD56+ cytotoxic cells from human umbilical cord blood. Exp Hematol 29: 104–113.

    Article  PubMed  CAS  Google Scholar 

  • Conneally E, Eaves CJ & Humphries RK (1998) Efficient retroviralmediated gene transfer to human cord blood stem cells with in vivo repopulating potential. Blood 91: 3487–3493.

    PubMed  CAS  Google Scholar 

  • Denning-Kendall PA, Evely R, Singha S, Chapman M, Bradley BA & Hows JM (2002) In vitro expansion of cord blood does not prevent engraftment of severe combined immunodeficient repopulating cells. Br J Haematol 116: 218–228.

    Article  PubMed  CAS  Google Scholar 

  • DiGiusto DL, Lee R, Moon J, Moss K, O'Toole T, Voytovich A, Webster D & Mule JJ (1996) Hematopoietic potential of cryopreserved and ex vivo manipulated umbilical cord blood progenitor cells evaluated in vitro and in vivo. Blood 87: 1261–1271.

    PubMed  CAS  Google Scholar 

  • Donaldson C, Denning-Kendall P, Bradley B & Hows J (2001) The CD34(+)CD38(neg) population is significantly increased in haemopoietic cell expansion cultures in serum-free compared to serum-replete conditions: Dissociation of phenotype and function. Bone Marrow Transplant 27: 365–371.

    Article  PubMed  CAS  Google Scholar 

  • Dorrell C, Gan OI, Pereira DS, Hawley RG & Dick JE (1999) Expansion of human cord blood CD34+CD38 cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: Dissociation of SRC phenotype and function. Blood 95: 102–110.

    Google Scholar 

  • Dravid G & Rao SG (2002) Ex vivo expansion of stem cells from umbilical cord blood: Expression of cell adhesion molecules. Stem Cells 20: 183–189.

    Article  PubMed  CAS  Google Scholar 

  • Erices A, Conget P & Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109: 235–242.

    Article  PubMed  CAS  Google Scholar 

  • Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G & Mavilio F (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279: 1528–1530.

    Article  PubMed  CAS  Google Scholar 

  • Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF & Keiliss-Borok IV (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17: 331–340.

    PubMed  CAS  Google Scholar 

  • Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J, Souillet G, Ferreira E, Laporte JP, Fernandez M & Chastang C (1997) Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 337: 373–381.

    Article  PubMed  CAS  Google Scholar 

  • Gluckman E (2000) Current status of umbilical cord blood hematopoietic stem cell transplantation. Exp Hematol 28: 1197–1205.

    Article  PubMed  CAS  Google Scholar 

  • Goodwin HS, Bicknese AR, Chien S-N, Bogucki BD, Oliver DA, Quinn CO & Wall DA (2001) Multilineage differentiation activity by cells isolated from umbilical cord blood: Expression of bone, fat and neural markers. Biol Blood Marrow Transplant 7: 581–588.

    Article  PubMed  CAS  Google Scholar 

  • Güenechea G, Segovia JC, Albella B, Lamana M, Ramírez M, Regidor C, Fernández MN & Bueren JA (1999) Delayed engraftment of Non Obese Diabetic/Severe Combined Immunodeficient mice transplanted with ex vivo-expanded human CD34+ cord blood cells. Blood 93: 1097–1105.

    PubMed  Google Scholar 

  • Guenechea G, Gan OI, Inamitsu T, Dorrell C, Pereira DS, Kelly M, Naldini L & Dick JE (2000) Transduction of human CD34+CD38– bone marrow and cord blood derived SCIDrepopulating cells with third generation lentiviral vectors. Mol Ther 1: 566–573.

    Article  PubMed  CAS  Google Scholar 

  • Gutiérrez-Rodríguez M, Reyes-Maldonado E & Mayani H (2000) Characterization of the adherent cells developed in Dexter-type long-term cultures from human umbilical cord blood. Stem Cells 18: 46–52.

    Article  PubMed  Google Scholar 

  • Ha Y, Choi, JU, Yoon DH, Yeon DS, Lee JJ, Kim HO & Cho YE (2001) Neural phenotype expression of cultured human cord blood cells in vitro. Neuroreport 12: 3523–3527.

    Article  PubMed  CAS  Google Scholar 

  • Henschler R, Brugger W, Luft T, Frey T, Mertelsmann R & Kanz L (1994) Maintenance of transplantation potential in ex vivo expanded CD34(+)-selected human peripheral blood progenitor cells. Blood 84: 2898–2903.

    PubMed  CAS  Google Scholar 

  • Hows JM, Bradley BA, Marsh JC, Luft T, Coutinho L, Testa NG & Dexter TM (1992) Growth of human umbilical-cord blood in longterm haemopoietic cultures. Lancet 340: 73–76.

    Article  PubMed  CAS  Google Scholar 

  • Hows JM (2001) Status of umbilical cord blood transplantation in the year 2001. J Clin Pathol 54: 428–434.

    Article  PubMed  CAS  Google Scholar 

  • Kohn DB, Hershfield MS, Carbonaro D, Shigeoka A, Brooks J, Smogorzewska EM, Barsky LW, Chan R, Burotto F, Annett G, Nolta JA, Crooks G, Kapoor N, Elder M, Wara D, Bowen T, Madsen E, Snyder FF, Bastian J, Muul L, Blaese RM, Weinberg K & Parkman R (1998) T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates. Nat Med 4: 775–780.

    Article  PubMed  CAS  Google Scholar 

  • Koller M, Manchel I, Maher R, Goltry K, Armstrong R & Smith A (1998) Clinical scale human umbilical cord blood cell expansion in a novel automated perfusion culture system. Bone Marrow Transplant 21: 653–663.

    Article  PubMed  CAS  Google Scholar 

  • Kopen GC, Prockop DJ & Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96: 10711–10716.

    Article  PubMed  CAS  Google Scholar 

  • Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC, Ciocci G, Carrier C, Stevens CE & Rubinstein P (1996) Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 335: 157–166.

    Article  PubMed  CAS  Google Scholar 

  • Lewis ID, Almeida-Poradr G, Du J, Lemischka IR, Moore KA, Zanjani ED & Verfaillie CM (2001) Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system. Blood 97: 3441–3449.

    Article  PubMed  CAS  Google Scholar 

  • Liu E, Tu W, Law HK & Lau YL (2001) Decreased yield, phenotypic expression and function of immature monocyte-derived dendritic cells in cord blood. Br J Haematol 113: 240–246.

    Article  PubMed  CAS  Google Scholar 

  • Liu A, Takahashi TM, Narita M, Zheng Z, Kanazawa N, Abe T, Nikkuni K, Furukawa T, Toba K, Fuse I & Aizawa Y (2002) Generation of functional and mature dendritic cells from cord blood and bone marrow CD34+ cells by two-step culture combined with calcium ionophore treatment. J Immunol Methods 261: 49–63.

    Article  PubMed  CAS  Google Scholar 

  • McNiece I, Kubegov D, Kerzic P, Shpall EJ & Gross S (2000) Increased expansion and differentiation of cord blood products using a two-step expansion culture. Exp Hematol 28: 1181–1186.

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi H, Smith KA, Mosier DE, Verma IM & Torbett BE (1999) Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science 283: 682–686.

    Article  PubMed  CAS  Google Scholar 

  • Murohara T (2001) Therapeutic vasculogenesis using human cord blood-derived endothelial progenitors. Trends Cardiovasc Medicine 11: 303–307.

    Article  CAS  Google Scholar 

  • Neildez-Nguyen TMA, Wajcman H, Marden MC, Bensidhoum M, Moncollin V, Giarratana M-C, Kobari L, Thierry D & Douay L (2002) Human erythroid cells produced ex vivo at large scale differentiate into red blood cells. Nat Biotech 20: 467–472.

    Article  CAS  Google Scholar 

  • Nieda M, Nicol A, Denning-Kendall P, Sweetenham J, Bradley B & Hows J (1997) Endothelial cell precursors are normal components of human umbilical cord blood. Br J Haematol 98: 775–777.

    Article  PubMed  CAS  Google Scholar 

  • Nishikawa SI (2001) A complex linkage in the developmental pathway of endothelial and hematopoietic cells. Curr Opin Cell Biol 13: 673–678.

    Article  PubMed  CAS  Google Scholar 

  • Ohkawara JI, Ikebuchi K, Fujihara M, Sato N, Hirayama F, Yamaguchi M, Mori KJ & Sekiguchi S (1998) Culture system for extensive production of CD19+IgM+ cells by human cord blood CD34+ progenitors. Leukemia 12: 764–771.

    Article  PubMed  CAS  Google Scholar 

  • Pereira RF, O'Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K & Prockop DJ (1998) Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci USA 95: 1142–1147.

    Article  PubMed  CAS  Google Scholar 

  • Piacibello W, Sanavio F, Garetto L, Severino A, Bergandi D, Ferrario J, Fagioli F, Berger M & Aglietta M (1997) Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood. Blood 89: 2644–2653.

    PubMed  CAS  Google Scholar 

  • Piacibello W, Sanavio F, Garetto L, Severino A, Dane A, Gammaitoni L & Aglietta M (1998) Differential growth factor requirement of primitive cord blood hematopoietic stem cell for self-renewal and amplification vs proliferation and differentiation. Leukemia 12: 718–727.

    Article  PubMed  CAS  Google Scholar 

  • Pick M, Nagler A, Grisaru D, Eldor A & Deutsch V (1998) Expansion of megaryocyte progenitors from human umbilical cord blood using a new two-step separation procedure. Br J Haematol 103: 639–650.

    Article  PubMed  CAS  Google Scholar 

  • Pick M, Eldor A, Grisaru D, Zander AR, Shenhav M & Deutsch VR (2002) Ex-vivo expansion of megakaryocyte progenitors from cryopreserved umbilical cord blood: A potential source of maegakaryocytes for transplantation. Exp Hematol 30: 1079–1087.

    Article  PubMed  Google Scholar 

  • Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276: 71–74.

    Article  PubMed  CAS  Google Scholar 

  • Robinson KL, Ayello J, Hughes R, van de Ven C, Issitt L, Kurtzberg J & Cairo MS (2002) Ex vivo expansion, maturation, and activation of umbilical cord blood-derived T lymphocytes with IL-2, IL-12, anti-CD3, and IL-7. Potential for adoptive cellular immunotherapy post-umbilical cord blood transplantation. Exp Hematol 30: 245–251.

    Article  PubMed  CAS  Google Scholar 

  • Salmon P, Kindler V, Ducrey O, Chapuis B, Zubler RH & Trono D (2000) High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood 96: 3392–3398.

    PubMed  CAS  Google Scholar 

  • Schilz AJ, Schiedlmeier B, Kuhlcke K, Fruehauf S, Lindemann C, Zeller WJ, Grez M, Fauser AA, Baum C & Eckert HG (2000) MDR1 gene expression in NOD/SCID repopulating cells after retroviral gene transfer under clinically relevant conditions. Mol Ther 2: 609–618.

    Article  PubMed  CAS  Google Scholar 

  • Shpall EJ, Quinones R, Giller R, Zeng C, Baron AE, Jones RB, Bearman SI, Nieto Y, Freed B, Madinger N, Hogan CJ, Slat-Vasquez V, Russell P, Blunk B, Schissel D, Hild E, Malcolm J, WardW & McNiece IK (2002) Transplantation of ex vivo expanded cord blood. Biol Blood Marrow Transplant 8: 368–376.

    Article  PubMed  Google Scholar 

  • Tao H, Gandry L, Rice A & Chong B (1999) Cord blood is better than bone marrow for generating megakaryocyte progenitor cells. Exp Hematol 27: 293–301.

    Article  PubMed  CAS  Google Scholar 

  • Traycoff CM, Abboud MR, Laver J, Clapp DW & Srour EF (1994) Rapid exit from G0/G1 phases of cell cycle in response to stem cell factor confers on umbilical cord blood CD34+ cells an enhanced ex vivo expansion potential. Exp Hematol 22: 1264–1272.

    PubMed  CAS  Google Scholar 

  • Traycoff CM, Kosak ST, Grigsby S & Srour EF (1995) Evaluation of ex vivo expansion potential of cord blood and bone marrow hematopoietic progenitor cells using cell tracking and limiting dilution analysis. Blood 85: 2059–2068.

    PubMed  CAS  Google Scholar 

  • Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay NK, McGlave PB, Sender L & Cairo MS (1996) Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: Analysis of engraftment and acute graft-versus-host disease. Blood 88: 795–802.

    PubMed  CAS  Google Scholar 

  • Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C, Goldman A, Kersey J, Krivit W, MacMillan ML, Orchard PJ, Peters C, Weisdorf DJ, Ramsay NKC & Davies SM (2002) Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: Influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 100: 1611–1618.

    PubMed  CAS  Google Scholar 

  • Woods N-B, Muessig A, Schmidt M, Flygare J, Olsson J, Salmon P, Trono D, Von Kalle C & Karlsson S (2000) Lentiviral vector transduction of NOD/SCID repopulating cells results in multiple vector integrations per transduced cell: risk of insertional mutagenesis. Blood 96: 3725–3733.

    PubMed  CAS  Google Scholar 

  • DeWynter E & Ploemacher RE (2001) Assays for the assessment of human hematopoietic stem cells. J Biol Regul Homeost Agents 15: 23–27.

    CAS  Google Scholar 

  • Zandstra PW, Conneally E, Petzer AL, Piret JM & Eaves CJ (1997) Cytokine manipulation of primitive human hematopoietic cell self-renewal. Proc Natl Acad Sci USA 94: 4698–4703.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Wynter, E.A. What is the future for cord blood stem cells?. Cytotechnology 41, 133–138 (2003). https://doi.org/10.1023/A:1024874706356

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1024874706356

Navigation