International Journal of Hematology

, Volume 92, Issue 1, pp 45–51 | Cite as

Stem and progenitor cells in human umbilical cord blood

  • Myoung Woo Lee
  • In Keun Jang
  • Keon Hee Yoo
  • Ki Woong Sung
  • Hong Hoe Koo
Review Article

Abstract

Both stem cells and progenitor cells are present in umbilical cord blood (UCB) at a high frequency, making these cells a major target population for experimental and clinical studies. As the use of autologous or allogeneic hematopoietic stem cell transplantation in the treatment of various diseases has grown rapidly in recent years, the concept of UCB banking for future use has drawn increasing interest. Stem and progenitor cells derived from UCB offer multiple advantages over adult stem cells, such as their immaturity (which may play a significant role in reducing rejection after transplantation into a mismatched host) and ability to produce large quantities of homogeneous tissue or cells. These cells can also differentiate across tissue lineage boundaries into neural, cardiac, epithelial, hepatic, and dermal tissues. Human UCB provides an alternative cell source that is ethically acceptable and widely supported by the public. This paper summarizes the characteristics of human UCB-derived stem and progenitor cells and their potential therapeutic use for tissue and cell regeneration.

Keywords

Umbilical cord blood Stem cells Progenitor cells 

References

  1. 1.
    Bianco P, Riminucci M, Kuznetsov S, Robey P. Multipotential cells in the bone marrow stroma: regulation in the context of organ physiology. Crit Rev Eukaryot Gene Expr. 1999;9:159–73.PubMedGoogle Scholar
  2. 2.
    Domen J, Weissman I. Self-renewal, differentiation or death: regulation and manipulation of hematopoietic stem cell fate. Mol Med Today. 1999;5:201–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Wu D, Schneiderman T, Burgett J, Gokhale P, Barthel L, Raymond P. Cones regenerate from retinal stem cells sequestered in the inner nuclear layer of adult goldfish retina. Invest Ophthalmol Vis Sci. 2001;42:2115–24.PubMedGoogle Scholar
  4. 4.
    Gandarillas A, Watt F. c-Myc promotes differentiation of human epidermal stem cells. Genes Dev. 1997;11:2869–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Seale P, Rudnicki M. A new look at the origin, function, and “stem-cell” status of muscle satellite cells. Dev Biol. 2000;218:115–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Gronthos S, Mankani M, Brahim J, Robey P, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 2000;97:13625–30.CrossRefPubMedGoogle Scholar
  7. 7.
    Sell S. Is there a liver stem cell? Cancer Res. 1990;50:3811–5.PubMedGoogle Scholar
  8. 8.
    Davis A, Temple S. A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature. 1994;372:263–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Kuehnle I, Goodell MA. The therapeutic potential of stem cells from adults. Br Med J. 2002;325:372–6.CrossRefGoogle Scholar
  10. 10.
    Rubinstein P, Rosenfield RE, Adamson JW, Stevens CE. Stored placental blood for unrelated bone marrow reconstruction. Blood. 1993;81:1679–90.PubMedGoogle Scholar
  11. 11.
    Gluckman E, Broxmeyer HA, Auerbach AD, Friedman HS, Douglas GW, Devergie A, Esperou H, Thierry D, Socie G, Lehn P, et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med. 1989;321:1174–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. Isolation of multi-potent mesenchymal stem cells from umbilical cord blood. Blood. 2004;103:1669–75.CrossRefPubMedGoogle Scholar
  13. 13.
    Lee MW, Choi J, Yang MS, Moon YJ, Park JS, Kim HC, Kim YJ. Mesenchymal stem cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2004;320:268–73.CrossRefGoogle Scholar
  14. 14.
    Kögler G, Sensken S, Airey JA, Trapp T, Muschen M, Feldhahn N, Liedtke S, Sorg RV, Fischer J, Rosenbaum C, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med. 2004;200:123–35.CrossRefPubMedGoogle Scholar
  15. 15.
    McGuckin CP, Forraz N, Allouard Q, Pettengell R. Umbilical cord blood stem cells can expand hematopoietic and neuroglial progenitors in vitro. Exp Cell Res. 2004;295:350–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Lee MW, Moon YJ, Yang MS, Kim SK, Jang IK, Eom Y, Park JS, Kim HC, Song KY, Park SC, Lim HS, Kim YJ. Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2007;358:637–43.CrossRefPubMedGoogle Scholar
  17. 17.
    Martin-Rendon E, Watt SM. Exploitation of stem cell plasticity. Transfus Med. 2003;13:325–48.CrossRefPubMedGoogle Scholar
  18. 18.
    Martin-Rendon E, Watt SM. Stem cell plasticity. Br J Haematol. 2003;122:877–91.CrossRefPubMedGoogle Scholar
  19. 19.
    Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci USA. 1994;91:9857–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Szilvassy SJ, Meyerrose TE, Ragland PL, Grimes B. Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver. Blood. 2001;98:2108–15.CrossRefPubMedGoogle Scholar
  21. 21.
    Waller EK, Olweus J, Lund-Johansen F, Huang S, Nguyen M, Guo GR, Terstappen L. The “common stem cell” hypothesis reevaluated: human fetal bone marrow contains separate populations of hematopoietic and stromal progenitors. Blood. 1995;85:2422–35.PubMedGoogle Scholar
  22. 22.
    Theilgaard-Mönch K, Raaschou-Jensen K, Schjødt K, Heilmann C, Vindeløv L, Jacobsen N, Dickmeiss E. Pluripotent and myeloid-committed CD34+ subsets in hematopoietic stem cell allografts. Bone Marrow Transplant. 2003;32:1125–33.CrossRefPubMedGoogle Scholar
  23. 23.
    Sutherland DR, Keating A. The CD34 antigen: structure, biology, and potential clinical applications. J Hematother. 1992;1:115–29.PubMedGoogle Scholar
  24. 24.
    Holyoake TL, Alcorn MJ. CD34+ positive haemopoietic cells: biology and clinical applications. Blood Rev. 1994;8:113–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Astori G, Adami V, Mambrini G, Bigi L, Cilli M, Facchini A, Falasca E, Malangone W, Panzani I, Degrassi A. Evaluation of ex vivo expansion and engraftment in NOD-SCID mice of umbilical cord blood CD34+ cells using the DIDECO “Pluricell System”. Bone Marrow Transplant. 2005;35:1101–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Flores-Guzman P, Gutierrez-Rodriguez M, Mayani H. In vitro proliferation, expansion, and differentiation of CD34+ cell-enriched hematopoietic cell population from human umbilical cord blood in response to recombinant cytokines. Arch Med Res. 2002;33:107–14.CrossRefPubMedGoogle Scholar
  27. 27.
    Guenechea G, Segovia JC, Albella B, Lamana M, Ramírez M, Regidor C, Fernández MN, Bueren JA. Delayed engraftment of nonobese diabetic/severe combined immunodeficient mice transplanted with ex vivo-expanded human CD34(+) cord blood cells. Blood. 1999;93:1097–105.PubMedGoogle Scholar
  28. 28.
    Tao W, Wang M, Voss ED, Cocklin RR, Smith JA, Cooper SH, Broxmeyer HE. Comparative proteomic analysis of human CD34+ stem/progenitor cells and mature CD15+ myeloid cells. Stem Cells. 2004;22:1003–14.CrossRefPubMedGoogle Scholar
  29. 29.
    Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, Fee F, Katsanakis KD, Rose DW, Mischak H, Sedivy JM, Kolch W. Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 1999;401:173–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Lorenz K, Lohse MJ, Quitterer U. Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature. 2003;426:574–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Hengst U, Albrecht H, Hess D, Monard D. The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors. J Biol Chem. 2001;276:535–40.CrossRefPubMedGoogle Scholar
  32. 32.
    Del Toro G, Satwani P, Harrison L, Cheung YK, Brigid Bradley M, George D, Yamashiro DJ, Garvin J, Skerrett D, Bessmertny O, Wolownik K, Wischhover C, van de Ven C, Cairo MS. A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients. Bone Marrow Transplant. 2004;33:613–22.CrossRefPubMedGoogle Scholar
  33. 33.
    Gluckman E, Broxmeyer HA, Auerbach AD, Friedman HS, Douglas GW, Devergie A, Esperou H, Thierry D, Socie G, Lehn P, et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med. 1989;321:1174–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Kim DW, Chung YJ, Kim TG, Kim YL, Oh IH. Cotransplantation of third-party mesenchymal stromal cells can alleviate single-donor predominance and increase engraftment from double cord transplantation. Blood. 2004;103:1941–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439–41.CrossRefPubMedGoogle Scholar
  36. 36.
    Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells. 2003;21:105–10.CrossRefPubMedGoogle Scholar
  37. 37.
    Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B, Hows JM. Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not. Br J Haematol. 2003;121:368–74.CrossRefPubMedGoogle Scholar
  38. 38.
    Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000;109:235–42.CrossRefPubMedGoogle Scholar
  39. 39.
    Rosada C, Justesen J, Melsvik D, Ebbesen P, Kassem M. The human umbilical cord blood: a potential source for osteoblast progenitor cells. Calcif Tissue Int. 2003;72:135–42.CrossRefPubMedGoogle Scholar
  40. 40.
    Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med. 2001;226:507–20.Google Scholar
  41. 41.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Lu L, Shen RN, Broxmeyer HE. Stem cells from bone marrow, umbilical cord blood and peripheral blood for clinical application: current status and future application. Crit Rev Oncol Hematol. 1996;22:61–78.CrossRefPubMedGoogle Scholar
  43. 43.
    Gutierrez-Rodriguez M, Reyes-Maldonado E, Mayani H. Characterization of the adherent cells developed in Dexter-type long-term cultures from human umbilical cord blood. Stem Cells. 2000;18:46–52.CrossRefPubMedGoogle Scholar
  44. 44.
    Yoo KH, Jang IK, Lee MW, Kim HE, Yang MS, Eom Y, Lee JE, Kim YJ, Yang SK, Jung HL, Sung KW, Kim CW, Koo HH. Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues. Cell Immunol. 2009;259:150–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Prockop DJ, Gregory CA, Spees JL. One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc Natl Acad Sci USA. 2003;100(Suppl.1):11917–23.CrossRefPubMedGoogle Scholar
  46. 46.
    Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002;416:542–5.CrossRefPubMedGoogle Scholar
  47. 47.
    Spees JL, Olson SD, Ylostalo J, Lynch PJ, Smith J, Perry A, Peister A, Wang MY, Prockop DJ. Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc Natl Acad Sci USA. 2003;100:2397–402.CrossRefPubMedGoogle Scholar
  48. 48.
    Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 2003;101:3722–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation. 2003;75:389–97.CrossRefPubMedGoogle Scholar
  50. 50.
    Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005;106:1755–61.CrossRefPubMedGoogle Scholar
  51. 51.
    Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA. 2003;100:8407–11.CrossRefPubMedGoogle Scholar
  52. 52.
    Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, Genrich K, Mehrotra S, Setty S, Smith B, Bartholomew A. IFN-γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008;38:1745–55.CrossRefPubMedGoogle Scholar
  53. 53.
    Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical use. Exp Hematol. 2000;28:875–84.CrossRefPubMedGoogle Scholar
  54. 54.
    Kögler G, Sensken S, Wernet P. Comparative generation and characterization of pluripotent unrestricted somatic stem cells with mesenchymal stem cells from human cord blood. Exp Hematol. 2006;34:1589–95.CrossRefPubMedGoogle Scholar
  55. 55.
    Kögler G, Radke TF, Lefort A, Sensken S, Fischer J, Sorg RV, Wernet P. Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol. 2005;33:573–83.CrossRefPubMedGoogle Scholar
  56. 56.
    Ghodsizad A, Niehaus M, Kögler G, Martin U, Wernet P, Bara C, Khaladj N, Loos A, Makoui M, Thiele J, Mengel M, Karck M, Klein HM, Haverich A, Ruhparwar A. Transplanted human cord blood-derived unrestricted somatic stem cells improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial infarction. Heart. 2009;95:27–35.CrossRefPubMedGoogle Scholar
  57. 57.
    Degistirici Ö, Jäger M, Knipper A. Applicability of cord blood-derived unrestricted somatic stem cells in tissue engineering concepts. Cell Prolif. 2008;41:421–40.CrossRefPubMedGoogle Scholar
  58. 58.
    Forraz N, Pettengell R, McGuckin CP. Characterization of a lineage-negative stem-progenitor cell population optimized for ex vivo expansion and enriched for LTC-IC. Stem Cells. 2004;22:100–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Gerrard L, Zhao D, Clark AJ, Cui W. Stably transfected human embryonic stem cell clones express OCT4-specific green fluorescent protein and maintain self-renewal and pluripotency. Stem Cells. 2005;23:124–33.CrossRefPubMedGoogle Scholar
  60. 60.
    McGuckin CP, Forraz N, Baradez MO, Navran S, Zhao J, Urban R, Tilton R, Denner L. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif. 2005;38:245–55.CrossRefPubMedGoogle Scholar
  61. 61.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.CrossRefPubMedGoogle Scholar
  62. 62.
    Matin MM, Walsh JR, Gokhale PJ, Draper JS, Bahrami AR, Morton I, Moore HD, Andrews PW. Specific knockdown of oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells. 2004;22:659–68.CrossRefPubMedGoogle Scholar
  63. 63.
    Hoffman LM, Carpenter MK. Characterization and culture of human embryonic stem cells. Nat Biotechnol. 2005;23:699–708.CrossRefPubMedGoogle Scholar
  64. 64.
    Davis T, Robinson D, Lee K, Kessler S. Porcine brain microvascular endothelial cells support the in vitro expansion of human primitive hematopoietic bone marrow progenitor cells with a high replanting potential: requirement for cell-to-cell interactions and colony-stimulating factors. Blood. 1995;85:1751–61.PubMedGoogle Scholar
  65. 65.
    Moon YJ, Lee MW, Yoon HH, Yang MS, Jang IK, Lee JE, Kim HE, Eom Y, Park JS, Kim HC, Kim YJ, Lee KH. Hepatic differentiation of cord blood-derived multipotent progenitor cells (MPCs) in vitro. Cell Biol Int. 2008;32:1293–301.CrossRefPubMedGoogle Scholar
  66. 66.
    Cho SR, Yang MS, Yim SH, Park JH, Lee JE, Eom YW, Jang IK, Kim HE, Park JS, Kim HO, Lee BH, Park CI, Kim YJ. Neurally induced umbilical cord blood cells modestly repair injured spinal cords. Neuroreport. 2008;19:1259–63.CrossRefPubMedGoogle Scholar
  67. 67.
    Moon YJ, Yoon HH, Lee MW, Jang IK, Lee DH, Lee JH, Lee SK, Lee KH, Kim YJ, Eom Y. Multipotent progenitor cells derived from human umbilical cord blood can differentiate into hepatocyte-like cells in a liver injury rat model. Transplant Proc. 2009;41:4357–60.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  • Myoung Woo Lee
    • 1
  • In Keun Jang
    • 1
  • Keon Hee Yoo
    • 1
  • Ki Woong Sung
    • 1
  • Hong Hoe Koo
    • 1
  1. 1.Department of Pediatrics, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea

Personalised recommendations