Umbilical Cord-Derived Mesenchymal Stem Cells

  • Jose J. MinguellEmail author


Hematopoiesis is a time- and site-dependent event ­during ontogeny of vertebrates. The first wave of hematopoietic activity appears in the ventral blood islands of the yolk sac, where primitive nucleated erythrocytes are formed to control the oxygen demand of the growing embryo. A second wave of primitive hematopoiesis (aorta-gonads-mesonephros, AGM region) is continued by a shift to the fetal liver where production of all hematopoietic cells is initiated. From near birth until the end of life, hematopoiesis resides in the bone marrow. Thus, embryonic, fetal, and adult hematopoieses are associated with a common stem cell, which, during each migratory event, reaches the specific milieu that is permissive for the programmed and sequential expression of the different forms of hematopoiesis.1


Mesenchymal Stem Cell Umbilical Cord Blood Fetal Liver Adult Bone Marrow Ductus Venosus 
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  1. 1.
    Tavassoli M. Embryonic and fetal hemopoiesis: an overview. Blood Cells. 1991;17:269-281.PubMedGoogle Scholar
  2. 2.
    Isern J, Fraser ST, He Z, Baron MH. The fetal liver is a niche for maturation of primitive erythroid cells. PNAS. 2008;105:6662-6667.CrossRefPubMedGoogle Scholar
  3. 3.
    Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haemat. 2000;109:235-242.CrossRefGoogle Scholar
  4. 4.
    Christensen JL, Wright DE, Wagers AJ, Weissman IL. Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol. 2004;2:e75.CrossRefPubMedGoogle Scholar
  5. 5.
    Kucia M, Reca R, Miekus K, et al. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1–CXCR4 axis. Stem Cells. 2005;23:879-894.CrossRefPubMedGoogle Scholar
  6. 6.
    Nguyen Huu S, Dubernard G, Aractingi S, Khosrotehrani K. Feto-maternal cell trafficking: a transfer of pregnancy associated progenitor cells. Stem Cell Rev. 2006;2:111-116.PubMedGoogle Scholar
  7. 7.
    Ara T, Tokoyoda K, Sugiyama T, Egawa T, Kawabata K, Nagasawa T. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity. 2003;19:257-267.CrossRefPubMedGoogle Scholar
  8. 8.
    Knudtzon S. In vitro growth of granulocyte colonies from circulating cells in human cord blood. Blood. 1974;43:357-361.PubMedGoogle Scholar
  9. 9.
    Leary AG, Ogawa M. Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors. Blood. 1987;69:953-956.PubMedGoogle Scholar
  10. 10.
    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;70:1324.CrossRefPubMedGoogle Scholar
  11. 11.
    Shields LE, Andrews RG. Gestational age changes in circulating CD34+ hematopoietic stem/progenitor cells in fetal cord blood. Am J Obstet Gynecol. 1998;178:931-937.CrossRefPubMedGoogle Scholar
  12. 12.
    Badillo AT, Flake AW. The regulatory role of stromal microenvironments in fetal hematopoietic ontogeny. Stem Cell Rev. 2006;2:241-246.CrossRefPubMedGoogle Scholar
  13. 13.
    Garcia Marquez G. Chronicle of a Death Foretold (A masterpiece novel by the Nobel Laureate in Literature). New York: Alfred A. Knopf; 1982.Google Scholar
  14. 14.
    Martin MA, Bhatia M. Analysis of the human fetal liver hematopoietic. Stem Cells Dev. 2005;14:493-504.CrossRefPubMedGoogle Scholar
  15. 15.
    Charbord P, Tavian M, Humeau L, Péault B. Early ontogeny of the human marrow from long bones: an immunohistochemical study of hematopoiesis and its microenvironment. Blood. 1996;88:4072-4078.Google Scholar
  16. 16.
    Heissig B, Ohki Y, Sato Y, Rafii S, Werb Z, Hattori K. A role for niches in hematopoietic cell development. Hematology. 2005;10(3):247-253.CrossRefPubMedGoogle Scholar
  17. 17.
    McGrath K, Palis J. Ontogeny of erythropoiesis in the mammalian embryo. Curr Top Dev Biol. 2008;82:1-22.CrossRefPubMedGoogle Scholar
  18. 18.
    Tavassoli M, Minguell JJ. Homing of hemopoietic rogenitor cells to the marrow. Proc Soc Exp Biol Med. 1991;196:367-373.PubMedGoogle Scholar
  19. 19.
    Weisel KC, Gao Y, Shieh JH, Moore MA. Stromal cell lines from the aorta-gonado-mesonephros region are potent supporters of murine and human hematopoiesis. Exp Hematol. 2006;34:1505-1516.CrossRefPubMedGoogle Scholar
  20. 20.
    Conget P, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol. 1999;181:67-73.CrossRefPubMedGoogle Scholar
  21. 21.
    Pittenger MF, Mackay AM, Beck CB, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143-147.CrossRefPubMedGoogle Scholar
  22. 22.
    Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 2004;22:625-634.CrossRefPubMedGoogle Scholar
  23. 23.
    Hutson EL, Boyer S, Genever PG. Rapid isolation, expansion, and differentiation of osteoprogenitors from full-term umbilical cord blood. Tissue Eng. 2005;11:1407-1420.CrossRefPubMedGoogle Scholar
  24. 24.
    Kim JW, Kim SY, Park SY, et al. Mesenchymal progenitor cells in the human umbilical cord. Ann Hematol. 2004;83:733.CrossRefPubMedGoogle Scholar
  25. 25.
    Markov V, Kusumi K, Tadesse MG, et al. Identification of cord blood-derived mesenchymal stem/stromal cell populations with distinct growth kinetics, differentiation potentials, and gene expression profiles. Stem Cells Dev. 2007;16:53-73.CrossRefPubMedGoogle Scholar
  26. 26.
    Parekkadan B, Sethu P, van Poll D, Yarmush ML, Toner M. Osmotic selection of human mesenchymal stem/progenitor cells from umbilical cord blood. Tissue Eng. 2007;13:2465-2473.CrossRefPubMedGoogle Scholar
  27. 27.
    Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med. 2001;226:507-520.Google Scholar
  28. 28.
    Roux S, Quinn J, Pichaud F, et al. Human cord blood monocytes undergo terminal osteoclast differentiation in vitro in the presence of culture medium conditioned by giant cell tumor of bone. J Cell Physiol. 1996;168:489-498.CrossRefPubMedGoogle Scholar
  29. 29.
    Yu M, Xiao Z, Shen L, Li L. Mid-trimester fetal blood-derived adherent cells share characteristics similar to mesenchymal stem cells but full-term umbilical cord blood does not. Br J Haematol. 2004;124:666-675.CrossRefPubMedGoogle Scholar
  30. 30.
    Wyrsch A, dalle Carbonare V, Jansen W, et al. Umbilical cord blood from preterm human fetuses is rich in committed and primitive hematopoietic progenitors with high proliferative and self-renewal capacity. Exp Hematol. 1999;27:1338-1345.CrossRefPubMedGoogle Scholar
  31. 31.
    Wang JF, Wang LJ, Wu YF, et al. Mesenchymal stem/progenitor cells in human umbilical cord blood as support for ex vivo expansion of CD34(+) hematopoietic stem cells and for chondrogenic differentiation. Haematologica. 2004;89:837-844.PubMedGoogle Scholar
  32. 32.
    Jeong JA, Gang EJ, Hong SH, et al. Rapid neural differentiation of human cord blood-derived mesenchymal stem cells. Neuroreport. 2004;15:1731-1734.CrossRefPubMedGoogle Scholar
  33. 33.
    Kang JH, Lee CK, Kim JR, et al. Estrogen stimulates the neuronal differentiation of human umbilical cord blood mesenchymal stem cells. Neuroreport. 2007;18:35-38.CrossRefPubMedGoogle Scholar
  34. 34.
    Li N, Feugier P, Serrurrier B, Latger-Cannard V, Lesesve JF, Stoltz JF. Human mesenchymal stem cells improve ex vivo expansion of adult human CD34+ peripheral blood ­progenitor cells and decrease their allostimulatory capacity. Exp Hematol. 2007;35:507-515.CrossRefPubMedGoogle Scholar
  35. 35.
    Wagner W, Wein F, Roderburg C, et al. Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell−cell interaction. Exp Hematol. 2007;35:314-332.CrossRefPubMedGoogle Scholar
  36. 36.
    Parolini O, Alviano F, Bagnara GP, et al. Isolation and characterization of cells from human term placenta. Stem Cells. 2008;26:300-311.CrossRefPubMedGoogle Scholar
  37. 37.
    Alviano F, Fossati V, Marchionni C, et al. Term Amniotic membrane is a high throughput source for multipotent ­mesenchymal stem cells with the ability to differentiate into endothelial cells in vitro. BMC Dev Biol. 2007;7:11.CrossRefPubMedGoogle Scholar
  38. 38.
    Portmann-Lanz CB, Schoeberlein A, Huber A, et al. Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol. 2006;194:664-673.CrossRefPubMedGoogle Scholar
  39. 39.
    Soncini M, Vertua E, Gibelli L, et al. Isolation and characterization of mesenchymal cells from human fetal membranes. J Tissue Eng Regen Med. 2007;1:296-305.CrossRefPubMedGoogle Scholar
  40. 40.
    Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis – supportive function and other potentials. Haematologica. 2006;91:1017-1026.PubMedGoogle Scholar
  41. 41.
    Kolf CM, Cho E, Tuan RS. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther. 2007;9:204.CrossRefPubMedGoogle Scholar
  42. 42.
    Minguell JJ, Erices A. Mesenchymal stem cells and the treatment of cardiac disease. Exp Biol Med. 2006;231:39-49.Google Scholar
  43. 43.
    Clinical trials, 2008. Identifier NCT # 00555828, 00548613, 00587990.
  44. 44.
    Feldmann RE Jr, Bieback K, Maurer MH, et al. Stem cell proteomes: a profile of human mesenchymal stem cells derived from umbilical cord blood. Electrophoresis. 2005;26:2749-2758.CrossRefPubMedGoogle Scholar
  45. 45.
    Yong KL, Fahey A, Pahal G, et al. Fetal haemopoietic cells display enhanced migration across endothelium. Br J Haematol. 2002;116:392-400.CrossRefPubMedGoogle Scholar
  46. 46.
    Erices EA, Allers CI, Conget PA, Rojas CV, Minguell JJ. Human cord blood-derived mesenchymal stem cells home and survive in the marrow of immunodeficient mice after systemic infusion. Cell Transplant. 2003;12:555-561.PubMedGoogle Scholar
  47. 47.
    Jäger M, Degistirici O, Knipper A, Fischer J, Sager M, Krauspe R. Bone healing and migration of cord ­blood-derived stem cells into a critical size femoral defect after ­xenotransplantation. J Bone Miner Res. 2007;22:1224-1233.CrossRefPubMedGoogle Scholar
  48. 48.
    Gotherstrom C, Ringden O, Westgren M, Tammik C, Le Blanc K. Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells. Bone Marrow Transplant. 2003;32:265-272.CrossRefPubMedGoogle Scholar
  49. 49.
    Gotherstrom C, Ringden O, Tammik C, Zetterberg E, Westgren M, Le Blanc K. Immunologic properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol. 2004;190:239-245.CrossRefPubMedGoogle Scholar
  50. 50.
    Tisato V, Naresh K, Girdlestone J, Navarrete C, Dazzi F. Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia. 2007;21:1992-1999.CrossRefPubMedGoogle Scholar
  51. 51.
    Reinisch A, Bartmann C, Rohde E, et al. Humanized system to propagate cord blood-derived multipotent mesenchymal stromal cells for clinical application. Regen Med. 2007;2:371-382.CrossRefPubMedGoogle Scholar

Copyright information

© Springer London 2011

Authors and Affiliations

  1. 1.TCA Cellular Therapy, LLCCovingtonUSA

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