Umbilical Cord Blood-Derived Endothelial Progenitor Cells for Cardiovascular Tissue Engineering

  • Benedikt Weber
  • Steffen M. Zeisberger
  • Hoerstrup Simon P. 


Term and preterm human umbilical cord blood (UCB) represents an easily accessible autologous and allogeneic cell source of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and endothelial colony forming cells (ECFCs, or alternatively outgrowing endothelial cells, OECs). All three cell types are regarded as valuable sources for regenerative medicine for pre- or postnatal therapies. In this section we would like to focus on endothelial progenitor cells (EPCs) used for cardiovascular tissue engineering purposes and ECFCs as example to investigate standardized chemically defined cell-culture protocols. Various cells originally identified as EPCs presented in various studies were and are in fact mostly hematopoietic cells (CD45+ progenitor cells, monocytes, platelets) that display angiogenic properties but are clearly distinct to rare circulating ECFCs or OECs (CD31+, CD34+, CD105+, CD146+, but 45−), since only ECFCs have the potential (in contrast to EPCs) of postnatal vasculogenic activity upon transplantation in a matrix scaffold. Because several different types of blood-derived endothelial cells are implicated as pro-angiogenic, future studies will be required to determine the exact role that each endothelial cell type plays in the process of vascular repair or regeneration. Up until now little is known of the in vivo functions of ECFCs in the many preclinical models of human cardiovascular disease and increased studies in this area may be illuminating. Recent studies revealed that infusion of ECFCs into pigs following experimentally induced acute myocardial infarction resulted in significant improvement in myocardial infarct remodeling and heart function via direct incorporation of the cells into the host endothelium. Also studies in murine models of retinal ischaemia showed that human ECFCs directly incorporate into the host murine vasculature, significantly decreasing avascular areas, concomitantly increasing normo-vascular areas and preventing pathologic pre-retinal neovascularization. In the field of cardiovascular regeneration and tissue engineering the endothelialization of constructs before implantation represents a crucial element of the fabrication process of potential implants to ensure lack of thrombogenicity in vivo. Therefore, UCB-EPCs have been intensively investigated in several in vitro studies for the fabrication of tissue engineered patches, vascular grafts and heart valves showing promising initial results. In vitro, the seeded UCB-EPCs showed a stable phenotype during static conditioning and the functionality of the cells was similar to mature vascular-derived endothelial cells. However, prior to a clinical translation of the concept, careful preclinical in vivo assessment of the UCB-EPC-based concept seems indispensable.


Heart Valve Umbilical Cord Blood Bovine Spongiform Encephalopathy Tissue Engineering Approach Umbilical Cord Blood Unit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Melero-Martin JM, et al. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res. 2008;103:194–202. doi: 10.1161/CIRCRESAHA.108.178590. pii: CIRCRESAHA.108.178590.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Cai H, et al. MnSOD marks cord blood late outgrowth endothelial cells and accompanies robust resistance to oxidative stress. Biochem Biophys Res Commun. 2006;350:364–9. doi: 10.1016/j.bbrc.2006.09.046. pii: S0006-291X(06)02075-4.PubMedCrossRefGoogle Scholar
  3. 3.
    Hirschi KK, Ingram DA, Yoder MC. Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2008;28:1584–95. doi: 10.1161/ATVBAHA.107.155960. pii: ATVBAHA.107.155960.PubMedCrossRefGoogle Scholar
  4. 4.
    Javed MJ, et al. Endothelial colony forming cells and mesenchymal stem cells are enriched at different gestational ages in human umbilical cord blood. Pediatr Res. 2008;64:68–73. doi: 10.1203/PDR.0b013e31817445e9.PubMedCrossRefGoogle Scholar
  5. 5.
    Ingram DA, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104:2752–60. doi: 10.1182/blood-2004-04-1396. pii: 2004-04-1396.PubMedCrossRefGoogle Scholar
  6. 6.
    Ingram DA, et al. Clonogenic endothelial progenitor cells are sensitive to oxidative stress. Stem Cells. 2007;25:297–304. doi: 10.1634/stemcells.2006-0340. pii: 2006-0340.PubMedCrossRefGoogle Scholar
  7. 7.
    Timmermans F, et al. Endothelial progenitor cells: identity defined? J Cell Mol Med. 2009;13:87–102. doi: 10.1111/j.1582-4934.2008.00598.x. pii: JCMM598.PubMedCrossRefGoogle Scholar
  8. 8.
    Yoder MC. Is endothelium the origin of endothelial progenitor cells? Arterioscler Thromb Vasc Biol. 2010;30:1094–103. doi: 10.1161/ATVBAHA.109.191635. pii: ATVBAHA.109.191635.PubMedCrossRefGoogle Scholar
  9. 9.
    Selvaggi TA, Walker RE, Fleisher TA. Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions. Blood. 1997;89:776–9.PubMedGoogle Scholar
  10. 10.
    Gulati R, et al. Diverse origin and function of cells with endothelial phenotype obtained from adult human blood. Circ Res. 2003;93:1023–5. doi: 10.1161/01.RES.0000105569.77539.21. pii: 01.RES.0000105569.77539.21.PubMedCrossRefGoogle Scholar
  11. 11.
    Yoder MC, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109:1801–9. doi: 10.1182/blood-2006-08-043471. pii: blood-2006-08-043471.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Zeisberger SM, et al. Optimization of the culturing conditions of human umbilical cord blood-derived endothelial colony-forming cells under xeno-free conditions applying a transcriptomic approach. Genes Cells. 2010;15:671–87. doi: 10.1111/j.1365-2443.2010.01409.x. pii: GTC1409.PubMedCrossRefGoogle Scholar
  13. 13.
    Rubin H. The disparity between human cell senescence in vitro and lifelong replication in vivo. Nat Biotechnol. 2002;20:675–81. doi: 10.1038/nbt0702-675. pii: nbt0702-675.PubMedCrossRefGoogle Scholar
  14. 14.
    Corselli M, et al. Clinical scale ex vivo expansion of cord blood-derived outgrowth endothelial progenitor cells is associated with high incidence of karyotype aberrations. Exp Hematol. 2008;36:340–9. doi: 10.1016/j.exphem.2007.10.008. pii: S0301-472X(07)00643-1.PubMedCrossRefGoogle Scholar
  15. 15.
    Reinisch A, et al. Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo. Blood. 2009;113:6716–25. doi: 10.1182/blood-2008-09-181362. pii: blood-2008-09-181362.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Janetzki S, et al. Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI). Cancer Immunol Immunother. 2008;57:303–15. doi: 10.1007/s00262-007-0380-6.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Mackensen A, Drager R, Schlesier M, Mertelsmann R, Lindemann A. Presence of IgE antibodies to bovine serum albumin in a patient developing anaphylaxis after vaccination with human peptide-pulsed dendritic cells. Cancer Immunol Immunother. 2000;49:152–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Tuschong L, Soenen SL, Blaese RM, Candotti F, Muul LM. Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy. Hum Gene Ther. 2002;13:1605–10. doi: 10.1089/10430340260201699.PubMedCrossRefGoogle Scholar
  19. 19.
    Martin MJ, Muotri A, Gage F, Varki A. Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med. 2005;11:228–32.PubMedCrossRefGoogle Scholar
  20. 20.
    Bradley R. Bovine spongiform encephalopathy and its relationship to the variant form of Creutzfeldt-Jakob disease. Contrib Microbiol. 2004;11:146–85.PubMedCrossRefGoogle Scholar
  21. 21.
    Will RG, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996;347:921–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Korhonen M. Culture of human mesenchymal stem cells in serum-free conditions: no breakthroughs yet. Eur J Haematol. 2007;78:167, author reply 168. doi:10.1111/j.1600-0609.2006.00785.x. pii: EJH785.Google Scholar
  23. 23.
    Asher DM. The transmissible spongiform encephalopathy agents: concerns and responses of United States regulatory agencies in maintaining the safety of biologics. Dev Biol Stand. 1999;100:103–18.PubMedGoogle Scholar
  24. 24.
    Reinisch A, Strunk D. Isolation and animal serum free expansion of human umbilical cord derived mesenchymal stromal cells (MSCs) and endothelial colony forming progenitor cells (ECFCs). J Vis Exp. 2009. doi: 10.3791/1525. pii: 1525.Google Scholar
  25. 25.
    Reinisch A, et al. Humanized system to propagate cord blood-derived multipotent mesenchymal stromal cells for clinical application. Regen Med. 2007;2:371–82. doi: 10.2217/17460751.2.4.371.PubMedCrossRefGoogle Scholar
  26. 26.
    Schallmoser K, et al. Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion. 2007;47:1436–46. doi: 10.1111/j.1537-2995.2007.01220.x. pii: TRF01220.PubMedCrossRefGoogle Scholar
  27. 27.
    Schallmoser K, Strunk D. Preparation of pooled human platelet lysate (pHPL) as an efficient supplement for animal serum-free human stem cell cultures. J Vis Exp. 2009. doi:10.3791/1523. pii: 1523.Google Scholar
  28. 28.
    St Croix B, et al. Genes expressed in human tumor endothelium. Science. 2000;289:1197–202. pii: 8729.PubMedCrossRefGoogle Scholar
  29. 29.
    Bagley RG, et al. Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248. Mol Cancer Ther. 2008;7:2536–46. doi: 10.1158/1535-7163.MCT-08-0050. pii: 7/8/2536.PubMedCrossRefGoogle Scholar
  30. 30.
    Phuc PV, et al. Isolation of three important types of stem cells from the same samples of banked umbilical cord blood. Cell Tissue Bank. 2012;13:341–51. doi: 10.1007/s10561-011-9262-4.PubMedCrossRefGoogle Scholar
  31. 31.
    Coldwell KE, et al. Effects of obstetric factors and storage temperatures on the yield of endothelial colony forming cells from umbilical cord blood. Angiogenesis. 2011;14:381–92. doi: 10.1007/s10456-011-9222-4.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Lin Y, Weisdorf DJ, Solovey A, Hebbel RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000;105:71–7. doi: 10.1172/JCI8071.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Vanneaux V, et al. In vitro and in vivo analysis of endothelial progenitor cells from cryopreserved umbilical cord blood: are we ready for clinical application? Cell Transplant. 2010;19:1143–55. doi: 10.3727/096368910X504487. pii: ct0014vanneaux.PubMedCrossRefGoogle Scholar
  34. 34.
    Schmidt D, et al. Prenatally fabricated autologous human living heart valves based on amniotic fluid derived progenitor cells as single cell source. Circulation. 2007;116:I64–70. doi: 10.1161/CIRCULATIONAHA.106.681494. pii: 116/11_suppl/I-64.PubMedCrossRefGoogle Scholar
  35. 35.
    Schmidt D, et al. Living autologous heart valves engineered from human prenatally harvested progenitors. Circulation. 2006;114:I125–31. doi: 10.1161/CIRCULATIONAHA.105.001040. pii: 114/1_suppl/I-125.PubMedCrossRefGoogle Scholar
  36. 36.
    Fischlein T, et al. In vitro endothelialization of a mesosystemic shunt: a clinical case report. J Vasc Surg. 1994;19:549–54. piii: S0741521494002405.PubMedCrossRefGoogle Scholar
  37. 37.
    Deutsch M, et al. Long-term experience in autologous in vitro endothelialization of infrainguinal ePTFE grafts. J Vasc Surg. 2009;49:352–62, discussion 362. doi:10.1016/j.jvs.2008.08.101. pii: S0741-5214(08)01509-7.Google Scholar
  38. 38.
    Meinhart JG, et al. Clinical autologous in vitro endothelialization of 153 infrainguinal ePTFE grafts. Ann Thorac Surg. 2001;71:S327–31.PubMedCrossRefGoogle Scholar
  39. 39.
    Fahy GM, Wowk B, Wu J. Cryopreservation of complex systems: the missing link in the regenerative medicine supply chain. Rejuvenation Res. 2006;9:279–91. doi: 10.1089/rej.2006.9.279.PubMedCrossRefGoogle Scholar
  40. 40.
    Gomez-Lechon MJ, et al. Evaluation of drug-metabolizing and functional competence of human hepatocytes incubated under hypothermia in different media for clinical infusion. Cell Transplant. 2008;17:887–97.PubMedCrossRefGoogle Scholar
  41. 41.
    Mason C, Manzotti E. Regenerative medicine cell therapies: numbers of units manufactured and patients treated between 1988 and 2010. Regen Med. 2010;5:307–13. doi: 10.2217/rme.10.37.PubMedCrossRefGoogle Scholar
  42. 42.
    Thirumala S, Zvonic S, Floyd E, Gimble JM, Devireddy RV. Effect of various freezing parameters on the immediate post-thaw membrane integrity of adipose tissue derived adult stem cells. Biotechnol Prog. 2005;21:1511–24. doi: 10.1021/bp050007q.PubMedCrossRefGoogle Scholar
  43. 43.
    Koc ON, et al. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant. 2002;30:215–22. doi: 10.1038/sj.bmt.1703650.PubMedCrossRefGoogle Scholar
  44. 44.
    Leberbauer C, et al. Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors. Blood. 2005;105:85–94. doi: 10.1182/blood-2004-03-1002. pii: 2004-03-1002.PubMedCrossRefGoogle Scholar
  45. 45.
    Parolini O, et al. Toward cell therapy using placenta-derived cells: disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table. Stem Cells Dev. 2010;19:143–54. doi: 10.1089/scd.2009.0404.PubMedCrossRefGoogle Scholar
  46. 46.
    Alencar S, et al. Cryopreservation of peripheral blood stem cell: the influence of cell concentration on cellular and hematopoietic recovery. Transfusion. 2010. doi:10.1111/j.1537-2995.2010.02743.x. pii: TRF2743.Google Scholar
  47. 47.
    Vrhovac R, et al. Post-thaw viability of cryopreserved hematopoietic progenitor cell grafts: does it matter? Coll Antropol. 2010;34:163–9.PubMedGoogle Scholar
  48. 48.
    Lu X, Proctor SJ, Dickinson AM. The effect of cryopreservation on umbilical cord blood endothelial progenitor cell differentiation. Cell Transplant. 2008;17:1423–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Miyamoto Y, Enosawa S, Takeuchi T, Takezawa T. Cryopreservation in situ of cell monolayers on collagen vitrigel membrane culture substrata: ready-to-use preparation of primary hepatocytes and ES cells. Cell Transplant. 2009;18:619–26.PubMedGoogle Scholar
  50. 50.
    Gimble JM, Guilak F, Bunnell BA. Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells. Stem Cell Res Ther. 2010;1:19. doi: 10.1186/scrt19. pii: scrt19.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;100:1249–60. doi: 10.1161/01.RES.0000265074.83288.09. pii: 100/9/1249.PubMedCrossRefGoogle Scholar
  52. 52.
    Thirumala S, Goebel WS, Woods EJ. Clinical grade adult stem cell banking. Organogenesis. 2009;5:143–54.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Brooke G, et al. Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials. Br J Haematol. 2009;144:571–9. doi: 10.1111/j.1365-2141.2008.07492.x. pii: BJH7492.PubMedCrossRefGoogle Scholar
  54. 54.
    Reinisch AI. Characteristics of six recent animal hoarding cases in Manitoba. Can Vet J. 2009;50:1069–73.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Gruen L, Grabel L. Concise review: scientific and ethical roadblocks to human embryonic stem cell therapy. Stem Cells. 2006;24:2162–9. doi: 10.1634/stemcells.2006-0105. pii: 2006-0105.PubMedCrossRefGoogle Scholar
  56. 56.
    Bielanski A, Bergeron H, Lau PC, Devenish J. Microbial contamination of embryos and semen during long term banking in liquid nitrogen. Cryobiology. 2003;46:146–52. pii: S0011224003000208.PubMedCrossRefGoogle Scholar
  57. 57.
    Hubalek Z. Protectants used in the cryopreservation of microorganisms. Cryobiology. 2003;46:205–29. pii: S0011224003000464.PubMedCrossRefGoogle Scholar
  58. 58.
    Reubinoff BE, Pera MF, Vajta G, Trounson AO. Effective cryopreservation of human embryonic stem cells by the open pulled straw vitrification method. Hum Reprod. 2011;16:2187–94.CrossRefGoogle Scholar
  59. 59.
    Matsumura K, Bae JY, Hyon SH. Polyampholytes as cryoprotective agents for mammalian cell cryopreservation. Cell Transplant. 2010. doi:10.3727/096368910X508780. pii: ct2254matsumura.Google Scholar
  60. 60.
    Junior AM, et al. Neurotoxicity associated with dimethylsulfoxide-preserved hematopoietic progenitor cell infusion. Bone Marrow Transplant. 2008;41:95–6. doi: 10.1038/sj.bmt.1705883. pii: 1705883.PubMedCrossRefGoogle Scholar
  61. 61.
    Rodrigues JP, et al. Evaluation of trehalose and sucrose as cryoprotectants for hematopoietic stem cells of umbilical cord blood. Cryobiology. 2008;56:144–51. doi: 10.1016/j.cryobiol.2008.01.003. pii: S0011-2240(08)00020-5.PubMedCrossRefGoogle Scholar
  62. 62.
    Windrum P, Morris TC. Severe neurotoxicity because of dimethyl sulphoxide following peripheral blood stem cell transplantation. Bone Marrow Transplant. 2005;31:315. doi: 10.1038/sj.bmt.1703848. pii: 1703848.CrossRefGoogle Scholar
  63. 63.
    Luciano AM, et al. Effect of different cryopreservation protocols on cytoskeleton and gap junction mediated communication integrity in feline germinal vesicle stage oocytes. Cryobiology. 2009;59:90–5. doi: 10.1016/j.cryobiol.2009.05.002. pii: S0011-2240(09)00062-5.PubMedCrossRefGoogle Scholar
  64. 64.
    Grein TA, et al. Alternatives to dimethylsulfoxide for serum-free cryopreservation of human mesenchymal stem cells. Int J Artif Organs. 2010;33:370–80. piii:0C7ABB72-1520-4971-A93E-030444E31D78.PubMedGoogle Scholar
  65. 65.
    Holm F, et al. An effective serum- and xeno-free chemically defined freezing procedure for human embryonic and induced pluripotent stem cells. Hum Reprod. 2010;25:1271–9. doi: 10.1093/humrep/deq040. pii: deq040.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Liu Y, et al. Cryopreservation of human bone marrow-derived mesenchymal stem cells with reduced dimethylsulfoxide and well-defined freezing solutions. Biotechnol Prog. 2010. doi: 10.1002/btpr.464.Google Scholar
  67. 67.
    Wagner K, Welch D. Cryopreserving and recovering of human iPS cells using complete knockout serum replacement feeder-free medium. J Vis Exp. 2010. doi:10.3791/2237. pii: 2237.Google Scholar
  68. 68.
    Gonzalez Hernandez Y, Fischer RW. Serum-free culturing of mammalian cells–adaptation to and cryopreservation in fully defined media. ALTEX. 2007;24:110–6.PubMedGoogle Scholar
  69. 69.
    Zeisberger SM, et al. Biological and physicochemical characterization of a serum- and xeno-free chemically defined cryopreservation procedure for adult human progenitor cells. Cell Transplant. 2011;20:1241–57. doi: 10.3727/096368910X547426. pii: ct0277zeisberger.PubMedCrossRefGoogle Scholar
  70. 70.
    Armitage WJ, Mazur P. Osmotic tolerance of human granulocytes. Am J Physiol. 1984;247:C373–81.PubMedGoogle Scholar
  71. 71.
    Meryman HT. Freezing injury and its prevention in living cells. Annu Rev Biophys Bioeng. 1974;3:341–63. doi: 10.1146/ Scholar
  72. 72.
    Iung B, Vahanian A. Epidemiology of valvular heart disease in the adult. Nat Rev Cardiol. 2011;8(3):162–72.PubMedCrossRefGoogle Scholar
  73. 73.
    Steinberg DH, Staubach S, Franke J, Sievert H. Defining structural heart disease in the adult patient: current scope, inherent challenges and future directions. Eur Heart J Suppl. 2010;12:E2–9.CrossRefGoogle Scholar
  74. 74.
    Schoen FJ. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation. 2008;118(18):1864–80.PubMedCrossRefGoogle Scholar
  75. 75.
    Weber B, Hoerstrup SP. Regenerating heart valves. In: Cohen IS, Gaudette GR, editors. Regenerating the heart: stem cells and the cardiovascular system. 1st ed. New York: Springer; 2011.Google Scholar
  76. 76.
    Langer R, Vacanti JP. Tissue engineering. Science. 1993;260:920–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Weber B, Falk V, Hoerstrup SP. Cardiovascular in situ tissue engineering. Cardiovasc Med. 2012;15(12):339–44.Google Scholar
  78. 78.
    Mol A, Smits AI, Bouten CV, Baaijens FP. Tissue engineering of heart valves: advances and current challenges. Expert Rev Med Devices. 2009;6(3):259–75.PubMedCrossRefGoogle Scholar
  79. 79.
    Mol A, Driessen NJ, Rutten MC, Hoerstrup SP, Bouten CV, Baaijens FP. Tissue engineering of human heart valve leaflets: a novel bioreactor for a strain-based conditioning approach. Ann Biomed Eng. 2005;33(12):1778–88.PubMedCrossRefGoogle Scholar
  80. 80.
    Roh JD, Sawh-Martinez R, Brennan MP, Jay SM, Devine L, Rao DA, Yi T, Mirensky TL, Nalbandian A, Udelsman B, Hibino N, Shinoka T, Saltzman WM, Snyder E, Kyriakides TR, Pober JS, Breuer CK. Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling. Proc Natl Acad Sci U S A. 2010;107:4669–74.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Schmidt D, Hoerstrup SP. Tissue engineered heart valves based on human cells. Swiss Med Wkly. 2006;136(39–40):618–23.PubMedGoogle Scholar
  82. 82.
    Shinoka T, Breuer CK, Tanel RE, Zund G, Miura T, Ma PX, Langer R, Vacanti JP, Mayer Jr JE. Tissue engineering heart valves: valve leaflet replacement study in a lamb model. Ann Thorac Surg. 1995;60(6 Suppl):S513–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Hoerstrup SP, Sodian R, Daebritz S, et al. Functional living trileaflet heart valves grown in vitro. Circulation. 2000;102(19 Suppl 3):III44–9.PubMedGoogle Scholar
  84. 84.
    Sutherland FW, Perry TE, Yu Y, et al. From stem cells to viable autologous semilunar heart valve. Circulation. 2005;111:2783–91.PubMedCrossRefGoogle Scholar
  85. 85.
    Schmidt D, Dijkman PE, Driessen-Mol A, Stenger R, Mariani C, Puolakka A, Rissanen M, Deichmann T, Odermatt B, Weber B, Emmert MY, Zund G, Baaijens FP, Hoerstrup SP. Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells. J Am Coll Cardiol. 2010;56(6):510–20.PubMedCrossRefGoogle Scholar
  86. 86.
    Dijkman PE, Driessen-Mol A, de Heer LM, Kluin J, van Herwerden LA, Odermatt B, Baaijens FP, Hoerstrup SP. Trans-apical versus surgical implantation of autologous ovine tissue-engineered heart valves. J Heart Valve Dis. 2012;21(5):670–8.PubMedGoogle Scholar
  87. 87.
    Weber B, Scherman J, Emmert MY, Gruenenfelder J, Verbeek R, Bracher M, Black M, Kortsmit J, Franz T, Schoenauer R, Baumgartner L, Brokopp C, Agarkova I, Wolint P, Zund G, Falk V, Zilla P, Hoerstrup SP. Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates. Eur Heart J. 2011;32(22):2830–40.PubMedCrossRefGoogle Scholar
  88. 88.
    Weber B, Emmert MY, Behr L, Schoenauer R, Brokopp C, Drögemüller C, Modregger P, Stampanoni M, Vats D, Rudin M, Bürzle W, Farine M, Mazza E, Frauenfelder T, Zannettino AC, Zünd G, Kretschmar O, Falk V, Hoerstrup SP. Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation. Biomaterials. 2012;33(16):4031–43.PubMedCrossRefGoogle Scholar
  89. 89.
    Dijkman PE, Driessen-Mol A, Frese L, Hoerstrup SP, Baaijens FP. Decellularized homologous tissueengineered heart valves as off-the-shelf alternatives to xeno- and homografts. Biomaterials. 2012;33(18):4545–54.PubMedCrossRefGoogle Scholar
  90. 90.
    Weber B, Dijkman PE, Scherman J, Sanders B, Emmert MY, Grünenfelder J, Verbeek R, Bracher M, Black M, Franz T, Kortsmit J, Modregger P, Peter S, Stampanoni M, Roberta J, Kehl D, van Doeselaar M, Schweiger M, Brokopp CE, Wälchli T, Falk V, Zilla P, Driessen-Mol A, Baaijens FPT, Hoerstrup SP. Off-the-shelf human decellularized tissue engineered heart valves in a non-human primate model. Biomaterials. 2013;34:7269–80.PubMedCrossRefGoogle Scholar
  91. 91.
    Weber B, Zeisberger SM, Hoerstrup SP. Prenatally harvested cells for cardiovascular tissue engineering: fabrication of autologous implants prior to birth. Placenta. 2011;32 Suppl 4:S316–9.PubMedCrossRefGoogle Scholar
  92. 92.
    Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, et al. Mesenchymal stem cells in Wharton’s jelly of the human umbilical cord. Stem Cells. 2004;22:1330–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Kögler G, Sensken S, Airey JA, Trapp T, Müschen M, Feldhahn N, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med. 2004;200:123–35.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Weiss ML, Anderson C, Medicetty S, et al. Immune properties of human umbilical cord Wharton’s jelly-derived cells. Stem Cells. 2008;26:2865–74.PubMedCrossRefGoogle Scholar
  95. 95.
    Schmidt D, Mol A, Neuenschwander S, Breymann C, Gössi M, Zund G, Turina M, et al. Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells. Eur J Cardiothorac Surg. 2005;27(5):795–800.PubMedCrossRefGoogle Scholar
  96. 96.
    Schmidt D, Asmis LM, Odermatt B, Kelm J, Breymann C, Gössi M, et al. Engineered living blood vessels: functional endothelia generated from human umbilical cord-derived progenitors. Ann Thorac Surg. 2006;82(4):1465–71.PubMedCrossRefGoogle Scholar
  97. 97.
    Schmidt D, Mol A, Odermatt B, Neuenschwander S, Breymann C, Gössi M, et al. Engineering of biologically active living heart valve leaflets using human umbilical cord-derived progenitor cells. Tissue Eng. 2006;12(11):3223–32.PubMedCrossRefGoogle Scholar
  98. 98.
    Sodian R, Lueders C, Kraemer L, Kuebler W, Shakibaei M, Reichart B, et al. Tissue engineering of autologous human heart valves using cryopreserved vascular umbilical cord cells. Ann Thorac Surg. 2006;81(6):2207–16.PubMedCrossRefGoogle Scholar
  99. 99.
    Weber B, Schoenauer R, Papadopulos F, Modregger P, Peter S, Stampanoni M, et al. Engineering of living autologous human umbilical cord cell-based septal occluder membranes using composite PGA-P4HB matrices. Biomaterials. 2011;32(36):9630–41.PubMedCrossRefGoogle Scholar
  100. 100.
    Megerian G, Ludomirsky A. Role of cordocentesis in perinatal medicine. Curr Opin Obstet Gynecol. 1994;6(1):30–5.PubMedGoogle Scholar
  101. 101.
    Weber B, Emmert MY, Hoerstrup SP. Stem cells for heart valve regeneration. Swiss Med Wkly. 2012;142:w13622.PubMedGoogle Scholar
  102. 102.
    Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000;109(1):235–42.PubMedCrossRefGoogle Scholar
  103. 103.
    Sodian R, Schaefermeier P, Abegg-Zips S, Kuebler WM, Shakibaei M, Daebritz S, et al. Use of human umbilical cord blood-derived progenitor cells for tissue-engineered heart valves. Ann Thorac Surg. 2010;89(3):819–28.PubMedCrossRefGoogle Scholar
  104. 104.
    Buchheiser A, Liedtke S, Looijenga LH, Kögler G. Cord blood for tissue regeneration. J Cell Biochem. 2009;108(4):762–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Schmidt D, Breymann C, Weber A, Guenter CI, Neuenschwander S, Zund G, Turina M, Hoerstrup SP. Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts. Ann Thorac Surg. 2004;78(6):2094–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Benedikt Weber
    • 1
  • Steffen M. Zeisberger
    • 1
  • Hoerstrup Simon P. 
    • 1
  1. 1.Swiss Center for Regenerative Medicine and Clinic for Cardiovascular Surgery, Division of Surgical ResearchUniversity Hospital Zurich, University of ZurichZurichSwitzerland

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