Abstract
Several stem and progenitor cells (SPCs) have been identified in human umbilical cord blood (UCB), bringing these unique cells as an important target for multitude experimental and clinical studies. Cord blood represents not only a rich source of applicable hematopoietic stem cells (HSCs) involved in hematopoietic and immunological system reconstitution but also an important reservoir of heterogeneous fraction of non-HSCs that may be utilized in regeneration of other tissue types. Such primitive SPCs belonging to non-hematopoietic compartment of UCB have been already described by several investigators and may include: very small embryonic-like stem cells (VSELs), endothelial progenitor cells (EPC), human UCB-neural stem cells (HUCB-NSC), unrestricted somatic stem cells (USSC), mesenchymal stem cells (MSC), multilineage progenitor cells, and other progenitor fractions. In some cases, vast similarities observed between those populations may indicate their possible fenotypic and functional overlap. In fact, some of non-hematopoietic UCB-derived SPCs may represent related fractions of primitive cells, but identified by various distinct experimental methods and protocols and eventually described as different populations.
UCB-derived non-HSC populations have been characterized according to their morphology, immunophenotype as well as proliferation and differentiation potentials. The biological immaturity, the ability to produce large quantities of homogeneous cells and to differentiate into a variety of specialized cell types, indicate the UCB-SPCs as suitable source of cells for cell-based therapies, regenerative medicine, and tissue engineering. Moreover, in case of human clinical specimens, UCB may be an alternative stem cell source that is ethically acceptable and easily available. This chapter focuses and summarizes the characteristics of selected human UCB-derived non-hematopoietic SPCs and their potential use for tissue and cell regeneration.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ali H, Al-Mulla F (2012) Defining umbilical cord blood stem cells. Stem Cell Discov 2:15–23
Ende M, Ende N (1972) Hematopoietic transplantation by means of fetal (cord) blood: a new method. Va Med Mon (1918) 99:276–280
Wang HS, Hung SC, Peng ST et al (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22:1330–1337
Semenov OV, Koestenbauer S, Riegel M et al (2010) Multipotent mesenchymal stem cells from human placenta: critical parameters for isolation and maintenance of stemness after isolation. Am J Obstet Gynecol 202:193.e1–193.e13
Vellasamy S, Sandrasaigaran P, Vidyadaran S et al (2012) Isolation and characterisation of mesenchymal stem cells derived from human placenta tissue. World J Stem Cells 4:53–61
Chevallier P, Robillard N, Illiaquer M et al (2013) Characterization of various blood and graft sources: a prospective series. Transfusion 53:2020–2026
Michejda M (2004) Which stem cells should be used for transplantation? Fetal Diagn Ther 19:2–8
Zhong XY, Zhang B, Asadollahi R et al (2010) Umbilical cord blood stem cells: what to expect. Ann N Y Acad Sci 1205:17–22
Mayani H (2011) Umbilical cord blood: lessons learned and lingering challenges after more than 20 years of basic and clinical research. Arch Med Res 42:645–651
Brunstein CG, Gutman JA, Weisdorf DJ et al (2010) Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 116:4693–4699
Scaradavou A, Brunstein CG, Eapen M et al (2013) Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia. Blood 121:752–758
Ratajczak MZ, Zuba-Surma EK, Machalinski B et al (2007) Bone-marrow-derived stem cells-our key to longevity? J Appl Genet 48:307–319
Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967
Kogler G, Sensken S, Airey JA et al (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200:123–135
McGuckin CP, Forraz N, Baradez MO et al (2005) Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif 38:245–255
Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74
Zuba-Surma EK, Kucia M, Ratajczak J et al (2009) “Small stem cells” in adult tissues: very small embryonic-like stem cells stand up! Cytometry A 75:4–13
Buzanska L, Machaj EK, Zablocka B et al (2002) Human cord blood-derived cells attain neuronal and glial features in vitro. J Cell Sci 115:2131–2138
Yoder MC, Mead LE, Prater D et al (2007) Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 109:1801–1809
Kucia M, Halasa M, Wysoczynski M et al (2007) Morphological and molecular characterization of novel population of CXCR4+SSEA-4+Oct-4+very small embryonic-like cells purified from human cord blood: preliminary report. Leukemia 21:297–303
Zuba-Surma EK, Klich I, Greco N et al (2010) Optimization of isolation and further characterization of umbilical-cord-blood-derived very small embryonic/epiblast-like stem cells (VSELs). Eur J Haematol 84:34–46
McGuckin C, Jurga M, Ali H et al (2008) Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro. Nat Protoc 3:1046–1055
Case J, Mead LE, Bessler WK et al (2007) Human CD34+AC133+VEGFR-2+cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol 35:1109–1118
Habich A, Jurga M, Markiewicz I et al (2006) Early appearance of stem/progenitor cells with neural-like characteristics in human cord blood mononuclear fraction cultured in vitro. Exp Hematol 34:914–925
Hou L, Cao H, Wang D et al (2003) Induction of umbilical cord blood mesenchymal stem cells into neuron-like cells in vitro. Int J Hematol 78:256–261
Lee OK, Kuo TK, Chen WM et al (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675
Lee MW, Moon YJ, Yang MS et al (2007) Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun 358:637–643
Knudtzon S (1974) In vitro growth of granulocytic colonies from circulating cells in human cord blood. Blood 43:357–361
Vaziri H, Dragowska W, Allsopp RC et al (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A 91:9857–9860
Mayani H, Lansdorp PM (1998) Biology of human umbilical cord blood-derived hematopoietic stem/progenitor cells. Stem Cells 16:153–165
Majeti R, Park CY, Weissman IL (2007) Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell 1:635–645
Buchheiser A, Liedtke S, Looijenga LH et al (2009) Cord blood for tissue regeneration. J Cell Biochem 108:762–768
Lee MW, Jang IK, Yoo KH et al (2010) Stem and progenitor cells in human umbilical cord blood. Int J Hematol 92:45–51
Pelosi E, Castelli G, Testa U (2012) Human umbilical cord is a unique and safe source of various types of stem cells suitable for treatment of hematological diseases and for regenerative medicine. Blood Cells Mol Dis 49:20–28
Kucia M, Reca R, Campbell FR et al (2006) A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia 20:857–869
Zuba-Surma EK, Kucia M, Abdel-Latif A et al (2008) Morphological characterization of very small embryonic-like stem cells (VSELs) by ImageStream system analysis. J Cell Mol Med 12:292–303
Zuba-Surma EK, Kucia M, Wu W et al (2008) Very small embryonic-like stem cells are present in adult murine organs: ImageStream-based morphological analysis and distribution studies. Cytometry A 73A:1116–1127
Ratajczak MZ, Zuba-Surma EK, Wysoczynski M et al (2008) Hunt for pluripotent stem cell—regenerative medicine search for almighty cell. J Autoimmun 30:151–162
Zuba-Surma EK, Wojakowski W, Ratajczak MZ et al (2011) Very small embryonic-like stem cells: biology and therapeutic potential for heart repair. Antioxid Redox Signal 15:1821–1834
Kucia M, Zuba-Surma EK, Wysoczynski M et al (2007) Adult marrow-derived very small embryonic-like stem cells and tissue engineering. Expert Opin Biol Ther 7:1499–1514
Bhartiya D, Shaikh A, Nagvenkar P et al (2012) Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy. Stem Cells Dev 21:1–6
Ratajczak J, Zuba-Surma E, Klich I et al (2011) Hematopoietic differentiation of umbilical cord blood-derived very small embryonic/epiblast-like stem cells. Leukemia 25:1278–1285
Zuba-Surma EK, Ratajczak MZ (2010) Overview of very small embryonic-like stem cells (VSELs) and methodology of their identification and isolation by flow cytometric methods. Current protocols in cytometry/editorial board, J Paul Robinson, managing editor [et al] Chap. 9:Unit9 29
Anand S, Bhartiya D, Sriraman K et al (2013) Quiescent very small embryonic-like stem cells resist oncotherapy and can restore spermatogenesis in germ cell depleted mammalian testis. Stem Cells Dev Sept 30
Sovalat H, Scrofani M, Eidenschenk A et al (2011) Identification and isolation from either adult human bone marrow or G-CSF-mobilized peripheral blood of CD34(+)/CD133(+)/CXCR4(+)/Lin(-)CD45(-) cells, featuring morphological, molecular, and phenotypic characteristics of very small embryonic-like (VSEL) stem cells. Exp Hematol 39:495–505
Iwaki R, Nakatsuka R, Matsuoka YM et al (2012) Development of a highly efficient method for isolating very small embryonic-like stem cells identified in adult mouse bone and their stem cell characteristics. (Abstract #2345). 54th ASH annual meeting (8–11 Dec 2012). Atlanta, GA, USA
Wojakowski W, Tendera M, Kucia M et al (2009) Mobilization of bone marrow-derived Oct-4+SSEA-4+ very small embryonic-like stem cells in patients with acute myocardial infarction. J Am Coll Cardiol 53:1–9
Paczkowska E, Kucia M, Koziarska D et al (2009) Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke. Stroke 40:1237–1244
Havens AM, Shiozawa Y, Jung Y et al (2013) Human very small embryonic-like cells generate skeletal structures, in vivo. Stem Cells Dev 22:622–630
Howe M, Zhao J, Bodenburg Y et al (2009) Oct-4 A isoform is expressed in human cord blood-derived CD133 stem cells and differentiated progeny. Cell Prolif 42:265–275
Danova-Alt R, Heider A, Egger D et al (2012) Very small embryonic-like stem cells purified from umbilical cord blood lack stem cell characteristics. PLoS ONE 7:e34899
Basile DP, Yoder MC (2014) Circulating and tissue resident endothelial progenitor cells. J Cell Physiol 229:10–16
Sieveking DP, Buckle A, Celermajer DS et al (2008) Strikingly different angiogenic properties of endothelial progenitor cell subpopulations: insights from a novel human angiogenesis assay. J Am Coll Cardiol 51:660–668
Rehman J (2011) Chipping away at the surface of the endothelial progenitor cell (EPC) mystery. J Mol Med (Berl) 89:943–945
Phuc PV, Ngoc VB, Lam DH et al (2012) Isolation of three important types of stem cells from the same samples of banked umbilical cord blood. Cell Tissue Bank 13:341–351
Shin JW, Lee DW, Kim MJ et al (2005) Isolation of endothelial progenitor cells from cord blood and induction of differentiation by ex vivo expansion. Yonsei Med J 46:260–267
Estes ML, Mund JA, Mead LE et al (2010) Application of polychromatic flow cytometry to identify novel subsets of circulating cells with angiogenic potential. Cytometry A 77:831–839
Lee JH, Lee SH, Yoo SY et al (2013) CD34 hybrid cells promote endothelial colony-forming cell bioactivity and therapeutic potential for ischemic diseases. Arterioscler Thromb Vasc Biol 33:1622–1634
Lin RZ, Dreyzin A, Aamodt K et al (2011) Functional endothelial progenitor cells from cryopreserved umbilical cord blood. Cell Transplant 20:515–522
Ladran I, Tran N, Topol A et al (2013) Neural stem and progenitor cells in health and disease. Wiley interdisciplinary reviews systems biology and medicine
Domanska-Janik K, Buzanska L, Lukomska B (2008) A novel, neural potential of non-hematopoietic human umbilical cord blood stem cells. Int J Dev Biol 52:237–248
Sun W, Buzanska L, Domanska-Janik K et al (2005) Voltage-sensitive and ligand-gated channels in differentiating neural stem-like cells derived from the nonhematopoietic fraction of human umbilical cord blood. Stem Cells 23:931–945
Jurga M, Lipkowski AW, Lukomska B et al (2009) Generation of functional neural artificial tissue from human umbilical cord blood stem cells. Tissue Eng Part C Methods 15:365–372
Zangiacomi V, Balon N, Maddens S et al (2008) Cord blood-derived neurons are originated from CD133+/CD34 stem/progenitor cells in a cell-to-cell contact dependent manner. Stem Cells Dev 17:1005–1016
Kogler G, Radke TF, Lefort A et al (2005) Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 33:573–583
Santourlidis S, Wernet P, Ghanjati F et al (2011) Unrestricted somatic stem cells (USSC) from human umbilical cord blood display uncommitted epigenetic signatures of the major stem cell pluripotency genes. Stem Cell Res 6:60–69
Buchheiser A, Houben AP, Bosch J et al (2012) Oxygen tension modifies the ‘stemness’ of human cord blood-derived stem cells. Cytotherapy 14:967–982
Kluth SM, Buchheiser A, Houben AP et al (2010) DLK-1 as a marker to distinguish unrestricted somatic stem cells and mesenchymal stromal cells in cord blood. Stem Cells Dev 19:1471–1483
Handschel J, Naujoks C, Langenbach F et al (2010) Comparison of ectopic bone formation of embryonic stem cells and cord blood stem cells in vivo. Tissue Eng Part A 16:2475–2483
Myers TJ, Granero-Molto F, Longobardi L et al (2010) Mesenchymal stem cells at the intersection of cell and gene therapy. Expert Opin Biol Ther 10:1663–1679
Chugh AR, Zuba-Surma EK, Dawn B (2009) Bone marrow-derived mesenchymal stems cells and cardiac repair. Minerva Cardioangiol 57:185–202
Bieback K, Kern S, Kluter H et al (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22:625–634
Flynn A, Barry F, O’Brien T (2007) UC blood-derived mesenchymal stromal cells: an overview. Cytotherapy 9:717–726
Carvalho MM, Teixeira FG, Reis RL et al (2011) Mesenchymal stem cells in the umbilical cord: phenotypic characterization, secretome and applications in central nervous system regenerative medicine. Curr Stem Cell Res Ther 6:221–228
Balasubramanian S, Venugopal P, Sundarraj S et al (2012) Comparison of chemokine and receptor gene expression between Wharton’s jelly and bone marrow-derived mesenchymal stromal cells. Cytotherapy 14:26–33
Forraz N, McGuckin CP (2011) The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Prolif 44(Suppl 1):60–69
Moon YJ, Lee MW, Yoon HH et al (2008) Hepatic differentiation of cord blood-derived multipotent progenitor cells (MPCs) in vitro. Cell Biol Int 32:1293–1301
Cho SR, Yang MS, Yim SH et al (2008) Neurally induced umbilical cord blood cells modestly repair injured spinal cords. Neuroreport 19:1259–1263
Moon YJ, Yoon HH, Lee MW et al (2009) Multipotent progenitor cells derived from human umbilical cord blood can differentiate into hepatocyte-like cells in a liver injury rat model. Transplant Proc 41:4357–4360
Acknowledgments
Supported by the European Union structural funds, Innovative Economy Operational Programme, grant No. POIG 01.02-00-109/09 “Innovative methods of stem cells applications in medicine” and Team grant (TEAM/2012-9/6) from the Foundation for Polish Science to EZS.3.6.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
Adamiak, M., Madeja, Z., Zuba-Surma, E. (2014). Cord Blood Stem Cells. In: Ratajczak, M. (eds) Adult Stem Cell Therapies: Alternatives to Plasticity. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1001-4_3
Download citation
DOI: https://doi.org/10.1007/978-1-4939-1001-4_3
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-1000-7
Online ISBN: 978-1-4939-1001-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)