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Modulation of Hematopoietic Stem/Progenitor Cell Migration

  • Thomas Dittmar
  • Susannah H. Kassmer
  • Benjamin Kasenda
  • Jeanette Seidel
  • Bernd Niggemann
  • Kurt S. Zänker
Chapter

Abstract

The ability to migrate is an innate and fundamental function of hematopoietic stem/progenitor cells (HSPCs) enabling them to leave and to return to the bone marrow, as well as to be recruited to injured tissues. The latter property of HSPCs concomitantly with their ability to transdifferentiate, thereby restoring the integrity of damaged tissues, raised great expectations for regenerative medicine purposes. It is well recognized that the migration of HSPCs is initiated and maintained by the chemokine stromal cell-derived factor-1α (SDF-1α). SDF-1α is expressed by bone marrow stroma cells, thereby generating a gradient, which directs the HSPC homing to the bone marrow. Likewise, SDF-1α is released by endothelial cells in close proximity of damaged organ tissue, thereby attracting HSPCs to sites of injury, which thereupon participate in tissue repair. It is of interest that most studies deal with the investigation of the SDF-1α-mediated induction of HSPC migration concomitantly with the decipherment of signal transduction cascades engaged by the SDF-1α receptor CXCR4. By contrast, considerably less is known about factors, conditions, and mechanisms that modulate the SDF-1α induced HSPC migration. Here we will give an overview about our research dealing with this topic and will show that the SDF-1α mediated migratory activity of cultured HSPCs strongly depends on the cytokines/cytokine combinations being used for HSPC cultivation. In fact, the removal of only one factor from a cytokine cocktail, which give rise to highly SDF-1α susceptible HSPCs, will yield in cells, which migratory activity is inhibited by SDF-1α. Additionally, we will also summarize our results concerning factors that might act as stop-signals for the SDF-1α induced migration of HSPCs, which may play a role in the termination of HSPC migration.

Keywords

Hematopoietic stem/Progenitor cells Cell migration Homing SDF-1α CXCR4 Signal transduction Termination of cell migration Culture conditions Cytokines Chemokines 

Notes

Acknowledgments

This work was supported by the Fritz-Bender-Foundation, Munich, Germany.

References

  1. 1.
    Terada N, Hamazaki T, Oka M, et al. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416: 542–545PubMedCrossRefGoogle Scholar
  2. 2.
    Grompe M (2003) The role of bone marrow stem cells in liver regeneration. Semin Liver Dis 23: 363–372PubMedCrossRefGoogle Scholar
  3. 3.
    Vassilopoulos G, Wang PR and Russell DW (2003) Transplanted bone marrow regenerates liver by cell fusion. Nature 422: 901–904PubMedCrossRefGoogle Scholar
  4. 4.
    Wang X, Willenbring H, Akkari Y, et al. (2003) Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422: 897–901PubMedCrossRefGoogle Scholar
  5. 5.
    Locatelli F, Corti S, Donadoni C, et al. (2003) Neuronal differentiation of murine bone marrow Thy-1- and Sca-1-positive cells. J Hematother Stem Cell Res 12: 727–734PubMedCrossRefGoogle Scholar
  6. 6.
    Mezey E and Chandross KJ (2000) Bone marrow: a possible alternative source of cells in the adult nervous system. Eur J Pharmacol 405: 297–302PubMedCrossRefGoogle Scholar
  7. 7.
    Mezey E, Chandross KJ, Harta G, et al. (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290: 1779–1782PubMedCrossRefGoogle Scholar
  8. 8.
    Camargo FD, Green R, Capetenaki Y, et al. (2003) Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat Med 9: 1520–1527PubMedCrossRefGoogle Scholar
  9. 9.
    Fukada S, Miyagoe-Suzuki Y, Tsukihara H, et al. (2002) Muscle regeneration by reconstitution with bone marrow or fetal liver cells from green fluorescent protein-gene transgenic mice. J Cell Sci 115: 1285–1293PubMedGoogle Scholar
  10. 10.
    Ferrari G, Cusella-De Angelis G, Coletta M, et al. (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279: 1528–1530PubMedCrossRefGoogle Scholar
  11. 11.
    Jackson KA, Majka SM, Wang H, et al. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107: 1395–1402PubMedCrossRefGoogle Scholar
  12. 12.
    Orlic D, Kajstura J, Chimenti S, et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410: 701–705PubMedCrossRefGoogle Scholar
  13. 13.
    Youn BS, Mantel C and Broxmeyer HE (2000) Chemokines, chemokine receptors and hematopoiesis. Immunol Rev 177: 150–174PubMedCrossRefGoogle Scholar
  14. 14.
    Thelen M (2001) Dancing to the tune of chemokines. Nat Immunol 2: 129–134PubMedCrossRefGoogle Scholar
  15. 15.
    Balabanian K, Lagane B, Infantino S, et al. (2005) The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem 280: 35760–35766PubMedCrossRefGoogle Scholar
  16. 16.
    Shirozu M, Nakano T, Inazawa J, et al. (1995) Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics 28: 495–500PubMedCrossRefGoogle Scholar
  17. 17.
    Yu L, Cecil J, Peng SB, et al. (2006) Identification and expression of novel isoforms of human stromal cell-derived factor 1. Gene 374: 174–179PubMedCrossRefGoogle Scholar
  18. 18.
    Gleichmann M, Gillen C, Czardybon M, et al. (2000) Cloning and characterization of SDF-1gamma, a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system. Eur J Neurosci 12: 1857–1866PubMedCrossRefGoogle Scholar
  19. 19.
    Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10: 858–864PubMedCrossRefGoogle Scholar
  20. 20.
    Rimland J, Xin W, Sweetnam P, et al. (1991) Sequence and expression of a neuropeptide Y receptor cDNA. Mol Pharmacol 40: 869–875PubMedGoogle Scholar
  21. 21.
    Federsppiel B, Melhado IG, Duncan AM, et al. (1993) Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen. Genomics 16: 707–712PubMedCrossRefGoogle Scholar
  22. 22.
    Loetscher M, Geiser T, O‘Reilly T, et al. (1994) Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem 269: 232–237PubMedGoogle Scholar
  23. 23.
    Feng Y, Broder CC, Kennedy PE, et al. (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272: 872–877PubMedCrossRefGoogle Scholar
  24. 24.
    Bleul CC, Farzan M, Choe H, et al. (1996) The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382: 829–833PubMedCrossRefGoogle Scholar
  25. 25.
    Oberlin E, Amara A, Bachelerie F, et al. (1996) The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382: 833–835PubMedCrossRefGoogle Scholar
  26. 26.
    Dittmar T, Heyder C, Gloria-Maercker E, et al. (2008) Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner. Clin Exp Metastasis 25: 11–32PubMedCrossRefGoogle Scholar
  27. 27.
    Hermann PC, Huber SL, Herrler T, et al. (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1: 313–323PubMedCrossRefGoogle Scholar
  28. 28.
    Zou YR, Kottmann AH, Kuroda M, et al. (1998) Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393: 595–599PubMedCrossRefGoogle Scholar
  29. 29.
    Ma Q, Jones D, Borghesani PR, et al. (1998) Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 95: 9448–9453PubMedCrossRefGoogle Scholar
  30. 30.
    Tachibana K, Hirota S, Iizasa H, et al. (1998) The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 393: 591–594PubMedCrossRefGoogle Scholar
  31. 31.
    Lapidot T, Dar A and Kollet O (2005) How do stem cells find their way home? Blood 106: 1901–1910PubMedCrossRefGoogle Scholar
  32. 32.
    Peled A, Petit I, Kollet O, et al. (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283: 845–848PubMedCrossRefGoogle Scholar
  33. 33.
    Kollet O, Shivtiel S, Chen YQ, et al. (2003) HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver. J Clin Invest 112: 160–169PubMedGoogle Scholar
  34. 34.
    Kollet O, Spiegel A, Peled A, et al. (2001) Rapid and efficient homing of human CD34(+)CD38(-/low)CXCR4(+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice. Blood 97: 3283–3291PubMedCrossRefGoogle Scholar
  35. 35.
    Brenner S, Whiting-Theobald N, Kawai T, et al. (2004) CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells. Stem Cells 22: 1128–1133PubMedCrossRefGoogle Scholar
  36. 36.
    Kahn J, Byk T, Jansson-Sjostrand L, et al. (2004) Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation. Blood 103: 2942–2949PubMedCrossRefGoogle Scholar
  37. 37.
    Kucia M, Jankowski K, Reca R, et al. (2004) CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol 35: 233–245PubMedCrossRefGoogle Scholar
  38. 38.
    Muller A, Homey B, Soto H, et al. (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410: 50–56PubMedCrossRefGoogle Scholar
  39. 39.
    Zlotnik A (2006) Chemokines and cancer. Int J Cancer 119: 2026–2029PubMedCrossRefGoogle Scholar
  40. 40.
    Heyder C, Gloria-Maercker E, Hatzmann W, et al. (2005) Role of the beta1-integrin subunit in the adhesion, extravasation and migration of T24 human bladder carcinoma cells. Clin Exp Metastasis 22: 99–106PubMedCrossRefGoogle Scholar
  41. 41.
    Bleul CC, Fuhlbrigge RC, Casasnovas JM, et al. (1996) A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 184: 1101–1109PubMedCrossRefGoogle Scholar
  42. 42.
    Aiuti A, Webb IJ, Bleul C, et al. (1997) 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 185: 111–120PubMedCrossRefGoogle Scholar
  43. 43.
    Kim CH and Broxmeyer HE (1998) In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow environment. Blood 91: 100–110PubMedGoogle Scholar
  44. 44.
    Ganju RK, Brubaker SA, Meyer J, et al. (1998) The alpha-chemokine, stromal cell-derived factor-1alpha, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways. J Biol Chem 273: 23169–23175PubMedCrossRefGoogle Scholar
  45. 45.
    Wang JF, Park IW and Groopman JE (2000) Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C. Blood 95: 2505–2513PubMedGoogle Scholar
  46. 46.
    Vila-Coro AJ, Rodriguez-Frade JM, Martin De Ana A, et al. (1999) The chemokine SDF-1alpha triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. FASEB J 13: 1699–1710PubMedGoogle Scholar
  47. 47.
    Lee Y, Gotoh A, Kwon HJ, et al. (2002) Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines. Blood 99: 4307–4317PubMedCrossRefGoogle Scholar
  48. 48.
    Clark EA and Brugge JS (1995) Integrins and signal transduction pathways: The road taken. Science 268: 233–239PubMedCrossRefGoogle Scholar
  49. 49.
    Dittmar T, Brandt BH, Lang K, et al. (2000) Lessons from tumor and immunocompetent cells. The quantitative engagement of ligand-receptor interactions modulates stop-and-go behavior as well as proliferation. Medicina (B. Aires) 60 (Suppl 2): 27–33Google Scholar
  50. 50.
    Dittmar T, Husemann A, Schewe Y, et al. (2002) Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR. FASEB J 16: 1823–1825PubMedGoogle Scholar
  51. 51.
    Entschladen F and Zänker KS (2000) Locomotion of tumor cells: a molecular comparison to migrating pre- and postmitotic leukocytes. J Cancer Res Clin Oncol 126: 671–681PubMedCrossRefGoogle Scholar
  52. 52.
    Fukuda S, Broxmeyer HE and Pelus LM (2005) Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1alpha(CXCL12)/CXCR4 axis. Blood 105: 3117–3126PubMedCrossRefGoogle Scholar
  53. 53.
    Petit I, Goichberg P, Spiegel A, et al. (2005) Atypical PKC-zeta regulates SDF-1-mediated migration and development of human CD34+ progenitor cells. J Clin Invest 115: 168–176PubMedGoogle Scholar
  54. 54.
    Mochly-Rosen D (1995) Localization of protein kinases by anchoring proteins: A theme in signal transduction. Science 268: 247–251PubMedCrossRefGoogle Scholar
  55. 55.
    Hofmann J (1997) The potential for isoenzyme-selective modulation of protein kinase C. FASEB J 11: 649–669PubMedGoogle Scholar
  56. 56.
    Cancelas JA, Lee AW, Prabhakar R, et al. (2005) Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med 11: 886–891PubMedCrossRefGoogle Scholar
  57. 57.
    Lapidot T (2001) Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF-1/CXCR4 interactions. Ann NY Acad Sci 938: 83–95PubMedCrossRefGoogle Scholar
  58. 58.
    Madri JA and Graesser D (2000) Cell migration in the immune system: the evolving inter-related roles of adhesion molecules and proteinases. Dev Immunol 7: 103–116PubMedCrossRefGoogle Scholar
  59. 59.
    Heyder C, Gloria-Maercker E, Hatzmann W, et al. (2006) Visualization of tumor cell extravasation. Contrib Microbiol 13: 200–208PubMedCrossRefGoogle Scholar
  60. 60.
    Spertini O, Cordey AS, Monai N, et al. (1996) P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+ hematopoietic progenitor cells. J Cell Biol 135: 523–531PubMedCrossRefGoogle Scholar
  61. 61.
    Naiyer AJ, Jo DY, Ahn J, et al. (1999) Stromal derived factor-1-induced chemokinesis of cord blood CD34(+) cells (long-term culture-initiating cells) through endothelial cells is mediated by E-selectin. Blood 94: 4011–4019PubMedGoogle Scholar
  62. 62.
    Papayannopoulou T, Craddock C, Nakamoto B, et al. (1995) The VLA4/VCAM-1 adhesion pathway defines contrasting mechanisms of lodgement of transplanted murine hemopoietic progenitors between bone marrow and spleen. Proc Natl Acad Sci USA 92: 9647–9651PubMedCrossRefGoogle Scholar
  63. 63.
    Papayannopoulou T, Priestley GV, Nakamoto B, et al. (2001) Molecular pathways in bone marrow homing: dominant role of alpha(4)beta(1) over beta(2)-integrins and selectins. Blood 98: 2403–2411PubMedCrossRefGoogle Scholar
  64. 64.
    Scott LM, Priestley GV and Papayannopoulou T (2003) Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing. Mol Cell Biol 23: 9349–9360PubMedCrossRefGoogle Scholar
  65. 65.
    Weidt C, Niggemann B, Kasenda B, et al. (2007) Stem cell migration: a quintessential stepping stone to successful therapy. Curr Stem Cell Res Treat 2: 89–103CrossRefGoogle Scholar
  66. 66.
    Bonig H, Wundes A, Chang KH, et al. (2008) Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab. Blood 111: 3439–3441PubMedCrossRefGoogle Scholar
  67. 67.
    Zohren F, Toutzaris D, Klarner V, et al. (2008) The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans. Blood 111: 3893–3895PubMedCrossRefGoogle Scholar
  68. 68.
    Peled A, Grabovsky V, Habler L, et al. (1999) The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest 104: 1199–1211PubMedCrossRefGoogle Scholar
  69. 69.
    Rosu-Myles M, Gallacher L, Murdoch B, et al. (2000) The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression. Proc Natl Acad Sci USA 97: 14626–14631PubMedCrossRefGoogle Scholar
  70. 70.
    Chang C and Werb Z (2001) The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol 11: S37–S43PubMedGoogle Scholar
  71. 71.
    Bar-Or A, Nuttall RK, Duddy M, et al. (2003) Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis. Brain 126: 2738–2749PubMedCrossRefGoogle Scholar
  72. 72.
    Yoon SO, Park SJ, Yun CH, et al. (2003) Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. J Biochem Mol Biol 36: 128–137PubMedCrossRefGoogle Scholar
  73. 73.
    Lapidot T and Petit I (2002) Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 30: 973–981PubMedCrossRefGoogle Scholar
  74. 74.
    Zheng Y, Sun A and Han ZC (2005) Stem cell factor improves SCID-repopulating activity of human umbilical cord blood-derived hematopoietic stem/progenitor cells in xenotransplanted NOD/SCID mouse model. Bone Marrow Transplant 35: 137–142PubMedCrossRefGoogle Scholar
  75. 75.
    Zheng Y, Watanabe N, Nagamura-Inoue T, et al. (2003) Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential. Exp Hematol 31: 1237–1246PubMedCrossRefGoogle Scholar
  76. 76.
    Weidt C, Niggemann B, Hatzmann W, et al. (2004) Differential effects of culture conditions on the migration pattern of stromal cell-derived factor-stimulated hematopoietic stem cells. Stem Cells 22: 890–896PubMedCrossRefGoogle Scholar
  77. 77.
    Seidel J, Niggemann B, Punzel M, et al. (2007) The neurotransmitter gamma-aminobutyric-acid (GABA) is a potent inhibitor of the stromal cell-derived factor-1. Stem Cells Dev 16: 827–836PubMedCrossRefGoogle Scholar
  78. 78.
    Kasenda B, Kassmer SH, Niggemann B, et al. (2008) The stromal cell-derived factor-1alpha dependent migration of human cord blood CD34 haematopoietic stem and progenitor cells switches from protein kinase C (PKC)-alpha dependence to PKC-alpha independence upon prolonged culture in the presence of Flt3-ligand and interleukin-6. Br J Haematol 142: 831–835PubMedCrossRefGoogle Scholar
  79. 79.
    Kollet O, Petit I, Kahn J, et al. (2002) Human CD34(+)CXCR4(-) sorted cells harbor intracellular CXCR4, which can be functionally expressed and provide NOD/SCID repopulation. Blood 100: 2778–2786PubMedCrossRefGoogle Scholar
  80. 80.
    Rose-John S (2003) Interleukin-6 biology is coordinated by membrane bound and soluble receptors. Acta Biochim Pol 50: 603–611PubMedGoogle Scholar
  81. 81.
    Nakashima S (2002) Protein kinase C alpha (PKC alpha): regulation and biological function. J Biochem 132: 669–675PubMedCrossRefGoogle Scholar
  82. 82.
    Martiny-Baron G, Kazanietz MG, Mischak H, et al. (1993) Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. J Biol Chem 268: 9194–9197PubMedGoogle Scholar
  83. 83.
    Fukuda S, Broxmeyer HE and Pelus LM (2005) Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1alpha (CXCL12)/CXCR4 axis. Blood 105: 3117–3126PubMedCrossRefGoogle Scholar
  84. 84.
    Audet J, Miller CL, Eaves CJ, et al. (2002) Common and distinct features of cytokine effects on hematopoietic stem and progenitor cells revealed by dose-response surface analysis. Biotechnol Bioeng 80: 393–404PubMedCrossRefGoogle Scholar
  85. 85.
    Ema H, Takano H, Sudo K, et al. (2000) In vitro self-renewal division of hematopoietic stem cells. J Exp Med 192: 1281–1288PubMedCrossRefGoogle Scholar
  86. 86.
    Miller CL and Eaves CJ (1997) Expansion in vitro of adult murine hematopoietic stem cells with transplantable lympho-myeloid reconstituting ability. Proc Natl Acad Sci USA 94: 13648–13653PubMedCrossRefGoogle Scholar
  87. 87.
    Ramsfjell V, Bryder D, Bjorgvinsdottir H, et al. (1999) Distinct requirements for optimal growth and In vitro expansion of human CD34(+)CD38(-) bone marrow long-term culture-initiating cells (LTC-IC), extended LTC-IC, and murine in vivo long-term reconstituting stem cells. Blood 94: 4093–4102PubMedGoogle Scholar
  88. 88.
    Piacibello W, Sanavio F, Severino A, et al. (1999) Engraftment in nonobese diabetic severe combined immunodeficient mice of human CD34(+) cord blood cells after ex vivo expansion: evidence for the amplification and self-renewal of repopulating stem cells. Blood 93: 3736–3749PubMedGoogle Scholar
  89. 89.
    Albella B, Segovia JC, Guenechea G, et al. (1999) Preserved long-term repopulation and differentiation properties of hematopoietic grafts subjected to ex vivo expansion with stem cell factor and interleukin 11. Transplantation 67: 1348–1357PubMedCrossRefGoogle Scholar
  90. 90.
    Cerny J, Dooner M, McAuliffe C, et al. (2002) Homing of purified murine lymphohematopoietic stem cells: a cytokine-induced defect. J Hematother Stem Cell Res 11: 913–922PubMedCrossRefGoogle Scholar
  91. 91.
    Ahmed F, Ings SJ, Pizzey AR, et al. (2004) Impaired bone marrow homing of cytokine-activated CD34+ cells in the NOD/SCID model. Blood 103: 2079–2087PubMedCrossRefGoogle Scholar
  92. 92.
    Von Drygalski A, Alespeiti G, Ren L, et al. (2004) Murine bone marrow cells cultured ex vivo in the presence of multiple cytokine combinations lose radioprotective and long-term engraftment potential. Stem Cells Dev 13: 101–111CrossRefGoogle Scholar
  93. 93.
    Kassmer SH, Niggemann B, Punzel M, et al. (2008) Cytokine combinations differentially influence the SDF-1alpha-dependent migratory activity of cultivated murine hematopoietic stem and progenitor cells. Biol Chem 389: 863–872PubMedCrossRefGoogle Scholar
  94. 94.
    Lang K, Hatt H, Niggemann B, et al. (2003) A novel function for chemokines: downregulation of neutrophil migration. Scand J Immunol 57: 350–361.PubMedCrossRefGoogle Scholar
  95. 95.
    Liesveld JL, Rosell K, Panoskaltsis N, et al. (2001) Response of human CD34+ cells to CXC, CC, and CX3C chemokines: implications for cell migration and activation. J Hematother Stem Cell Res 10: 643–655PubMedCrossRefGoogle Scholar
  96. 96.
    Rane MJ, Gozal D, Butt W, et al. (2005) Gamma-amino butyric acid type B receptors stimulate neutrophil chemotaxis during ischemia-reperfusion. J Immunol 174: 7242–7249PubMedGoogle Scholar
  97. 97.
    Steidl U, Bork S, Schaub S, et al. (2004) Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. Blood 104: 81–88PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Thomas Dittmar
    • 1
  • Susannah H. Kassmer
    • 2
  • Benjamin Kasenda
    • 3
  • Jeanette Seidel
    • 4
  • Bernd Niggemann
    • 5
  • Kurt S. Zänker
    • 5
  1. 1.Institute of Immunology, Witten/Herdecke UniversityWittenGermany
  2. 2.Department of Laboratory MedicineYale Stem Cell Center, Yale UniversityNew HavenUSA
  3. 3.Department of Hematology and OncologyUniversity of Freiburg Medical CenterFreiburgGermany
  4. 4.Medizinische Klinik II m. S. Hämatologie/OnkologieBerlinGermany
  5. 5.Institute of Immunology, Witten/Herdecke UniversityWittenGermany

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