Characterization and ex vivo expansion umbilical cord bloodhematopoietic stem and progenitor cells

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Abstract

Umbilical cord blood as an alternative source of hematopoietic stem and progenitor cells is widely used in clinical practice. Thereby it is necessary to characterize hematopoietic progenitors and to define among them the most «primitive» cells with the greatest repopulating potential. In addition absolute number of hematopoietic stem and progenitor cells is limited, so it is important to find ways of increasing their ex vivo. Currently several methods of in vitro and in vivo characterize hematopoietic progenitors and of ex vivo expansion of these cells have been developed. In this review we describe this methods, as well as problems with their translation to the clinical transplantation.

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A. I Ufimtceva

«Trans-Technologies Ltd», Saint-Petersburg

E. V Kanov

«Trans-Technologies Ltd», Saint-Petersburg

References

  1. Thomas E.D., Lochte H.L., Lu W.C. et al. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N. Engl. J. Med. 1957; 257(11): 491-6.
  2. Till J.E., McCulloch E.A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 1961; 14: 213-22.
  3. Forsberg E.C., Prohaska S.S., Katzman S. et al. Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genet. 2005; 1(3): e28.
  4. Schoemans H., Verfaillie C. Cellular biology of hematopoiesis. In: Hoffman R., Benz E.J., Shattil S.J. et al., editors. Hematology: Basic Principles and Practice. 5th edn. Part III. Philadelphia: Elsevier Churchill Livingston; 2008: 358-71.
  5. Alenzi F.Q., Alenazi B.Q., Ahmad S.Y. et al. The haemopoietic stem cell: between apoptosis and self renewal. Yale J. Biol. Med. 2009; 82(1): 7-18.
  6. Zhu J., Emerson S.G. Hematopoietic cytokines, transcription factors and lineage commitment. Oncogene 2002; 21(21): 3295-313.
  7. Dahl R., Hromas R. Transcription factors in normal and malignant hematopoiesis. In: Hoffman R., Benz E.J. Jr., Shattil S.J. et al., editors. Hematology: Basic Principles and Practice. 5th edn. Part III. Philadelphia: Elsevier Churchill Livingston; 2008: 372-95.
  8. Lessard J., Faubert A., Sauvageau G. Genetic programs regulating HSC specification, maintenance and expansion. Oncogene 2004; 23(43): 7199-209.
  9. Haylock D.N., Nilsson S.K. Stem cell regulation by the hematopoietic stem cell niche. Cell Cycle 2005; 4: 1353-5. ского применения. Однако необходимо решить целый ряд технических задач для культивирования клеток в объемах, которые требуются для трансплантации. Кроме того, важен строгий контроль применяемых методик для обеспечения безопасности пациентов.
  10. Zhang C.C., Lodish H.F. Cytokines regulating hematopoietic stem cell function. Curr. Opin. Hematol. 2008; 15(4): 307-11.
  11. Oh I.H., Kwon K.R. Concise review: multiple niches for hematopoietic stem cell regulations. Stem Cells 2010; 28(7): 1243-9.
  12. Arai F., Hirao A., Ohmura M. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004; 118(2): 149-61.
  13. Cerdan C., Bhatia M. Novel roles for Notch, Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells. Int. J. Dev. Biol. 2010; 54(6-7): 955-63.
  14. Delaney C., Ratajczak M.Z., Laughlin M.J. Strategies to enhance umbilical cord blood stem cell engraftment in adult patients. Expert. Rev. Hematol. 2010; 3(3): 273-83.
  15. Hofmeister C.C., Zhang J., Knight K.L. et al. Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche. Bone Marrow Transplant. 2007; 39(1): 11-23.
  16. Peled A., Petit I., Kollet O. et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 1999; 283(5403): 845-8.
  17. Aiuti A., Webb I.J., Bleul C. et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J. Exp. Med. 1997; 185(1): 111-20.
  18. Peled A., Kollet O., Ponomaryov T. et al. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34( + ) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 2000; 95(11): 3289-96.
  19. Avigdor A., Goichberg P., Shivtiel S. et al. CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/ progenitor cells to bone marrow. Blood 2004; 103(8): 2981—9.
  20. Christopherson K.W., Hangoc G., Broxmeyer H.E. Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J. Immunol. 2002; 169(12): 7000—8.
  21. Krause D.S., Fackler M.J., Civin C.I. et al. CD34: structure, biology, and clinical utility. Blood 1996; 87(1): 1—13.
  22. Sutherland D.R., Anderson L., Keeney M. et al. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J. Hematother. 1996; 5(3): 213—26.
  23. Craig W., Kay R., Cutler R.L. et al. Expression of Thy-1 on human hematopoietic progenitor cells. J. Exp. Med. 1993; 177(5): 1331—42.
  24. Yin A.H., Miraglia S., Zanjani E.D. et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997; 90(12): 5002—12.
  25. Encabo A., Mateu E., Carbonell-Uberos F. et al. CD34 + CD38- is a good predictive marker of cloning ability and expansion potential of CD34+ cord blood cells. Transfusion 2003; 43(3): 383—9.
  26. Zanjani E.D., Almeida-Porada G., Livingston A.G. et al. Human bone marrow CD34— cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp. Hematol. 1998; 26(4): 353—60.
  27. Bhatia M., Bonnet D., Murdoch B. et al. A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat. Med. 1998; 4(9): 1038—45.
  28. Goodell M.A., Rosenzweig M., Kim H. et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat. Med. 1997; 3(12): 1337—45.
  29. Wang J., Kimura T., Asada R. et al. SCID-repopulating cell activity of human cord blood-derived CD34- cells assured by intra-bone marrow injection. Blood 2003; 101(8): 2924—31.
  30. Sonoda Y. Immunophenotype and functional characteristics of human primitive CD34-negative hematopoietic stem cells: the significance of the intra-bone marrow injection. J. Autoimmun. 2008; 30(3): 136—44.
  31. Yahata T., Ando K., Sato T. et al. A highly sensitive strategy for SCID-repopulating cell assay by direct injection of primitive human hematopoietic cells into NOD/SCID mice bone marrow. Blood 2003; 101(8): 2905—13.
  32. Kimura T., Asada R., Wang J. et al. Identification of long-term repopulating potential of human cord blood-derived CD34-flt3- severe combined immunodeficiency-repopulating cells by intra-bone marrow injection. Stem Cells 2007; 25(6): 1348—55.
  33. Chen C.Z., Li M., de Graaf D. et al. Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells. PNAS USA 2002; 99(24): 15468—73.
  34. Balazs A.B., Fabian A.J., Esmon C.T. et al. Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow. Blood 2006; 107(6): 2317—21.
  35. Wagers A.J. Stem cell grand SLAM. Cell 2005; 121(7): 967—70.
  36. Challen G.A., Little M.H. A side order of stem cells: the SP phenotype. Stem Cells 2006; 24: 3.
  37. Goodell M.A., Brose K., Paradis G. et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 1996; 183(4): 1797—806.
  38. Liu H., Verfaillie C.M. Myeloid-lymphoid initiating cells (ML-IC) are highly enriched in the rhodamine-c-kit( + )CD33(-)CD38(-) fraction of umbilical cord CD34( + ) cells. Exp. Hematol. 2002; 30: 582.
  39. McKenzie J.L., Takenaka K., Gan O.I. et al. Low rhodamine 123 retention identifies long-term human hematopoietic stem cells within the Lin-CD34+CD38- population. Blood 2007; 109: 543.
  40. Arai F., Hirao A., Suda T. Regulation of hematopoietic stem cells by the niche. Trends Cardiovasc. Med. 2005; 15(2): 75—9.
  41. Pierre-Louis O., Clay D., Brunet de la Grange P. et al. Dual SP/ALDH functionalities refine the human hematopoietic Lin- CD34+CD38— stem/progenitor cell compartment. Stem Cells 2009; 27(10): 2552—62.
  42. Hess D.A., Meyerrose T.E., Wirthlin L. et al. Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood 2004; 104(6): 1648—55.
  43. Christ O., Lucke K., Imren S. et al. Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity. Haematologica 2007; 92(9): 1165—72.
  44. Lioznov M.V., Freiberger P., Kroger N. et al. Aldehyde dehydrogenase activity as a marker for the quality of hematopoietic stem cell transplants. Bone Marrow Transplant. 2005; 35(9): 909—14.
  45. Fallon P., Gentry T., Balber A.E. et al. Mobilized peripheral blood SSCloALDHbr cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation. Br. J. Haematol. 2003; 122: 99—108.
  46. Yang H., Acker J.P., Cabuhat M. et al. Association of postthaw viable CD34+ cells and CFU-GM with time to hematopoietic engraftment. Bone Marrow Transplant. 2005; 35(9): 881—7.
  47. International standards for cord blood collection, processing, testing, banking, selection, and release. 3rd Edn; 2006.
  48. Nadali G., de Wynter E.A., Perandin F. et al. Regulation of the proliferative potential of cord blood long-term culture-initiating cells (LTC-IC) by different stromal cell lines: implications for LTC-IC measurement. Haematologica 1998; 83(12): 1059—65.
  49. Denning-Kendall P., Singha S., Bradley B. et al. Cobblestone area-forming cells in human cord blood are heterogeneous and differ from long-term culture-initiating cells. Stem Cells 2003; 21(6): 694—701.
  50. Bhatia M., Wang J.C., Kapp U. et al. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. PNAS USA 1997; 94(10): 5320—5.
  51. Chao N.J., Emerson S.G., Weinberg K.I. Stem cell transplantation (cord blood transplants). Hematology Am. Soc. Hematol. Educ. Program. 2004; 354—71.
  52. Gammaitoni L., Weisel K.C., Gunetti M. et al. Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication. Blood 2004; 103(12): 4440—8.
  53. Harris D.T., Schumacher M.J., Locascio J. et al. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. PNAS USA 1992; 89(21): 10006—10.
  54. Rocha V., Gluckman E. Eurocord-Netcord registry and European Blood and Marrow Transplant group. Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factors. Br. J. Haematol. 2009; 147(2): 262—74.
  55. Koestenbauer S., Zisch A., Dohr G. et al. Protocols for hematopoietic stem cell expansion from umbilical cord blood. Cell Transplant. 2009; 18(10): 1059—68.
  56. Gluckman E., Rocha V. Cord blood transplantation: state of the art. Haematologica 2009; 94(4): 451—4.
  57. Laughlin M.J., Eapen M., Rubinstein P. et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N. Engl. J. Med. 2004; 351(22): 2265—75.
  58. Gilner J.B., Walton W.G., Gush K. et al. Antibodies to stem cell marker antigens reduce engraftment of hematopoietic stem cells. Stem Cells 2007; 25(2): 279—88.
  59. Kobayashi M., Laver J.H., Lyman S.D. et al. Thrombopoietin, steel factor and the ligand for flt3/flk2 interact to stimulate the proliferation of human hematopoietic progenitors in culture. Int. J. Hematol. 1997; 66(4): 423—34.
  60. Herrera C., Sanchez J., Torres A. et al. Early-acting cytokine- driven ex vivo expansion of mobilized peripheral blood CD34+ cells generates post-mitotic offspring with preserved engraftment ability in non-obese diabetic/severe combined immunodeficient mice. Br. J. Haematol. 2001; 114(4): 920—30.
  61. Zandstra P.W., Conneally E., Petzer A.L. et al. Cytokine manipulation of primitive human hematopoietic cell self-renewal. PNAS USA 1997; 94(9): 4698—703.
  62. Berger M., Fagioli F., Piacibello W. et al. Role of different medium and growth factors on placental blood stem cell expansion: an in vitro and in vivo study. Bone Marrow Transplant. 2002; 29(5): 443—8.
  63. Henschler R., Brugger W., Luft T. et al. Maintenance of transplantation potential in ex vivo expanded CD34( + )-selected human peripheral blood progenitor cells. Blood 1994; 84(9): 2898—903.
  64. Kobari L., Pflumio F., Giarratana M. et al. In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34+ cord blood cells. Exp. Hematol. 2000; 28(12): 1470—80.
  65. Donaldson C., Denning-Kendall P., Bradley B. et al. 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. 2001; 27(4): 365—71.
  66. Shpall E.J., Quinones R., Giller R. et al. Transplantation of ex vivo expanded cord blood. Biol. Blood Marrow Transplant. 2002; 8(7): 368—76.
  67. Mohamed A.A., Ibrahim A.M., El-Masry M.W. et al. Ex vivo expansion of stem cells: defining optimum conditions using various cytokines. Lab. Hematol. 2006; 12(2): 86—93
  68. Robinson S.N., Ng J., Niu T. et al. Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cell. Bone Marrow Transplant. 2006; 37(4): 359—66.
  69. Wagner W., Roderburg C., Wein F. et al. Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells 2007; 25(10): 2638—47.
  70. Kadereit S., Deeds L.S., Haynesworth S.E. et al. Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34+/CD38— early progenitors cultured over human mscs as a feeder layer. Stem Cells 2002; 20(6): 573—82.
  71. Mishima S., Nagai A., Abdullah S. et al. Effective ex vivo expansion of hematopoietic stem cells using osteoblast-differentiated mesenchymal stem cells is CXCL12 dependent. Eur. J. Haematol. 2010; 84(6): 538-46.
  72. Jang Y.K., Jung D.H., Jung M.H. et al. Mesenchymal stem cells feeder layer from human umbilical cord blood for ex vivo expanded growth and proliferation of hematopoietic progenitor cells. Ann. Hematol. 2006; 85(4): 212-25.
  73. Yildirim S., Boehmler A.M., Kanz L. et al. Expansion of cord blood CD34+ hematopoietic progenitor cells in coculture with autologous umbilical vein endothelial cells (HUVEC) is superior to cytokine-supplemented liquid culture. Bone Marrow Transplant. 2005; 36(1): 71-9.
  74. Ehring B., Biber T.M., Upton T.M. et al. Expansion of HPCs from cord blood in a novel 3D matrix. Cytotherapy 2003; 5: 490-9.
  75. Feng Q., Chai C., Jiang X.S. et al. Expansion of engrafting human hematopoietic stem/progenitor cells in three-dimensional scaffolds with surfaceimmobilized fibronectin. J. Biomed. Mater. Res. 2006; 78: 781-91.
  76. Takagi M., Iemoto N., Yoshida T. Effect of concentrations of murine stromal and hematopoietic cells on the progenitors expansion in their three-dimensional coculture in nonwoven fabrics. J. Biosci. Bioeng. 2002; 94(4): 365-7.
  77. Okamoto T., Takagi M., Soma T. et al. Effect of heparin addition on expansion of cord blood hematopoietic progenitor cells in threedimensional coculture with stromal cells in nonwoven fabrics. J. Artif. Organs. 2004; 7(4): 194-202.
  78. Purton L.E., Bernstein I.D., Collins S.J. All-trans retinoic acid delays the differentiation of primitive hematopoietic precursors (lin-c-kit + Sca-1( + )) while enhancing the terminal maturation of committed granulocyte/monocyte progenitors. Blood 1999; 94(2): 483-95.
  79. Peled T., Landau E., Prus E. et al. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood- derived CD34+ cells. Br. J. Haematol. 2002; 116(3): 655-61.
  80. Boitano A.E., Wang J., Romeo R. et al. Cooke M.P. aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 2010; 329(5997): 1345-8.
  81. Delaney C., Heimfeld S., Brashem-Stein C. et al. Notch- mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat. Med. 2010; 16(2): 232-6.
  82. Drake A.C., Khoury M., Leskov I. et al. Human CD34+ CD133+ hematopoietic stem cells cultured with growth factors including angptl5 efficiently engraft adult NOD-SCID Il2rc2/2 (NSG) mice. PLoS One 2011; 6(4): e18382.
  83. Trevis A., Peled T., Rosen O., inventors; Gamida-Cell Ltd., assignee. Ex-vivo expansion of hematopoietic stem cell populations in mononuclear cell cultures. AU patent 2005200679. 2005 Feb16.
  84. De Felice L., Tatarelli C., Mascolo M.G. et al. Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Cancer Res. 2005; 65(4): 1505-13.
  85. Milhem M., Mahmud N., Lavelle D. et al. Modification of hematopoietic stem cell fate by 5aza 2'deoxycytidine and trichostatin A. Blood 2004; 103(11): 4102-10.
  86. Yang M., Li K., Ng P.C. et al. Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and antiapoptosis. Stem Cells 2007; 25(7): 1800-6.
  87. Himburg H.A., Muramoto G.G., Daher P. et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat. Med. 2010; 16(4): 475-82.
  88. Pirih F.Q., Michalski M.N., Cho S.W. et al. Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6. PLoS One 2010; 5(10): e13657.
  89. Kowalczyk M., Waldron K., Kresnowati P. Process challenges relating to hematopoietic stem cell cultivation in bioreactors. J. Ind. Microbiol. Biotechnol. 2011; 38(7): 761-7.
  90. Nielsen L.K. Bioreactors for hematopoietic cell culture. Annu. Rev. Biomed. Eng. 1999; 1: 129-52
  91. de Lima M., McMannis J., Gee A. et al. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant. 2008; 41(9): 771-8.

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