Stem Cell Reviews and Reports

, Volume 7, Issue 3, pp 590–607 | Cite as

The Ins and Outs of Hematopoietic Stem Cells: Studies to Improve Transplantation Outcomes

  • Leah A. Marquez-Curtis
  • A. Robert Turner
  • Santhi Sridharan
  • Mariusz Z. Ratajczak
  • Anna Janowska-WieczorekEmail author


Deciphering the mechanisms of hematopoietic stem/progenitor cell (HSPC) mobilization and homing is important for the development of strategies to enhance the efficacy of HSPC transplantation and achieve the full potential of HSPC-based cellular therapy. Investigation of these mechanisms has revealed interdependence among the various molecules, pathways and cellular components involved, and underscored the complex nature of these two processes. This review summarizes recent progress in identifying the specific factors implicated in HSPC mobilization and homing, with emphasis on our own work. Particularly, we will discuss our studies on stromal cell-derived factor-1 and its interaction with its receptor CXCR4, proteases (matrix metalloproteinases and carboxypeptidase M), complement proteins (C1q, C3a, C5a, membrane attack complex), sphingosine-1-phosphate, and pharmacologic agents such as the histone deacetylase inhibitor valproic acid and hyaluronic acid.


Hematopoietic stem cells Mobilization Homing Transplantation 



Our research on “Mechanisms of HSPC Mobilization and Homing” has been funded by an operating grant (XE00025) from the Canadian Blood Services (CBS) Research and Development/Canadian Institutes for Health Research Blood Utilization and Conservation Partnership Initiative to AJW and a National Institutes of Health grant (ROI CA105847) to MZR. We thank the staff of the Stem Cell Transplant Program and the CBS Stem Cell Processing Laboratory in Edmonton for procurement of patient samples.

The authors declare no potential conflicts of interest.


  1. 1.
    Appelbaum, F. R. (2007). Hematopoietic-cell transplantation at 50. New England Journal of Medicine, 357, 1472–1475.PubMedCrossRefGoogle Scholar
  2. 2.
    Barrett, A. J., Longhurst, P., Sneath, P., & Watson, J. G. (1978). Mobilization of CFU-C by exercise and ACTH induced stress in man. Experimental Hematology, 6, 590–594.PubMedGoogle Scholar
  3. 3.
    Richman, C. M., Weiner, R. S., & Yankee, R. A. (1976). Increase in circulating stem cells following chemotherapy in man. Blood, 47, 1031–1039.PubMedGoogle Scholar
  4. 4.
    To, L. B., Haylock, D. N., Simmons, P. J., & Juttner, C. A. (1997). The biology and clinical uses of blood stem cells. Blood, 89, 2233–2258.PubMedGoogle Scholar
  5. 5.
    Gazitt, Y. (2004). Homing and mobilization of hematopoietic stem cells and hematopoietic cancer cells are mirror image processes, utilizing similar signaling pathways and occurring concurrently: circulating cancer cells constitute an ideal target for concurrent treatment with chemotherapy and antilineage-specific antibodies. Leukemia, 18, 1–10.PubMedCrossRefGoogle Scholar
  6. 6.
    Schofield, R. (1978). The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells, 4, 7–25.PubMedGoogle Scholar
  7. 7.
    Jones, D. L., & Wagers, A. J. (2008). No place like home: anatomy and function of the stem cell niche. Nature Reviews Molecular Cell Biology, 9, 11–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Raaijmakers, M. H., & Scadden, D. T. (2008). Evolving concepts on the microenvironmental niche for hematopoietic stem cells. Current Opinion in Hematology, 15, 301–306.PubMedCrossRefGoogle Scholar
  9. 9.
    Calvi, L. M., Adams, G. B., Weibrecht, K. W., et al. (2003). Osteoblastic cells regulate the haematopoietic stem cell niche. Nature, 425, 841–846.PubMedCrossRefGoogle Scholar
  10. 10.
    Kiel, M. J., Yilmaz, O. H., Iwashita, T., Terhorst, C., & Morrison, S. J. (2005). SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell, 121, 1109–1121.PubMedCrossRefGoogle Scholar
  11. 11.
    Xie, Y., Yin, T., Wiegraebe, W., et al. (2009). Detection of functional haematopoietic stem cell niche using real-time imaging. Nature, 457, 97–101.PubMedCrossRefGoogle Scholar
  12. 12.
    Taichman, R. S., Reilly, M. J., & Emerson, S. G. (1996). Human osteoblasts support human hematopoietic progenitor cells in in vitro bone marrow cultures. Blood, 87, 518–524.PubMedGoogle Scholar
  13. 13.
    Taichman, R. S. (2005). Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood, 105, 2631–2639.PubMedCrossRefGoogle Scholar
  14. 14.
    Lévesque, J. P., Helwani, F. M., & Winkler, I. G. (2010). The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia. Sep 23 [Epub ahead of print].Google Scholar
  15. 15.
    Winkler, I. G., Barbier, V., Wadley, R., Zannettino, A. C., Williams, S., & Levesque, J. P. (2010). Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches. Blood, 116, 375–385.PubMedCrossRefGoogle Scholar
  16. 16.
    Abkowitz, J. L., Robinson, A. E., Kale, S., Long, M. W., & Chen, J. (2003). Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood, 102, 1249–1253.PubMedCrossRefGoogle Scholar
  17. 17.
    Kopp, H. G., Avecilla, S. T., Hooper, A. T., & Rafii, S. (2005). The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology (Bethesda), 20, 349–356.Google Scholar
  18. 18.
    Winkler, I. G., Sims, N. A., Pettit, A. R., et al. (2010). Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSC. Blood, Aug 16 [Epub ahead of print].Google Scholar
  19. 19.
    Mendez-Ferrer, S., Michurina, T. V., Ferraro, F., et al. (2010). Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature, 466, 829–834.PubMedCrossRefGoogle Scholar
  20. 20.
    Aiuti, A., Webb, I. J., Bleul, C., Springer, T., & Gutierrez-Ramos, J. C. (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. Journal of Experimental Medicine, 185, 111–120.PubMedCrossRefGoogle Scholar
  21. 21.
    Wright, D. E., Bowman, E. P., Wagers, A. J., Butcher, E. C., & Weissman, I. L. (2002). Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. Journal of Experimental Medicine, 195, 1145–1154.PubMedCrossRefGoogle Scholar
  22. 22.
    Ponomaryov, T., Peled, A., Petit, I., et al. (2000). Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. Journal of Clinical Investigation, 106, 1331–1339.PubMedCrossRefGoogle Scholar
  23. 23.
    Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., et al. (2004). Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nature Medicine, 10, 858–864.PubMedCrossRefGoogle Scholar
  24. 24.
    Lapidot, T., & Petit, I. (2002). Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Experimental Hematology, 30, 973–981.PubMedCrossRefGoogle Scholar
  25. 25.
    Cottler-Fox, M. H., Lapidot, T., Petit, I., et al. (2003). Stem cell mobilization. Hematology American Society of Hematology Education Program, 419–437.Google Scholar
  26. 26.
    Papayannopoulou, T. (2004). Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization. Blood, 103, 1580–1585.PubMedCrossRefGoogle Scholar
  27. 27.
    Levesque, J. P., & Winkler, I. G. (2008). Mobilization of hematopoietic stem cells: state of the art. Current Opinion in Organ Transplantation, 13, 53–58.PubMedCrossRefGoogle Scholar
  28. 28.
    Papayannopoulou, T., & Scadden, D. T. (2008). Stem-cell ecology and stem cells in motion. Blood, 111, 3923–3930.PubMedCrossRefGoogle Scholar
  29. 29.
    Pelus, L. M. (2008). Peripheral blood stem cell mobilization: new regimens, new cells, where do we stand. Current Opinion in Hematology, 15, 285–292.PubMedCrossRefGoogle Scholar
  30. 30.
    Schulz, C., von Andrian, U. H., & Massberg, S. (2009). Hematopoietic stem and progenitor cells: their mobilization and homing to bone marrow and peripheral tissue. Immunologic Research, 44, 160–168.PubMedCrossRefGoogle Scholar
  31. 31.
    Ratajczak, M. Z., Kim, C. H., Wojakowski, W., Janowska-Wieczorek, A., Kucia, M., & Ratajczak, J. (2010). Innate immunity as orchestrator of stem cell mobilization. Leukemia, 24, 1667–1675.PubMedCrossRefGoogle Scholar
  32. 32.
    Gertz, M. (2010). Current status of stem cell mobilization. British Journal of Haematology, 150, 647–662.PubMedCrossRefGoogle Scholar
  33. 33.
    Winkler, I. G., & Levesque, J. P. (2006). Mechanisms of hematopoietic stem cell mobilization: when innate immunity assails the cells that make blood and bone. Experimental Hematology, 34, 996–1009.PubMedCrossRefGoogle Scholar
  34. 34.
    Bensinger, W., DiPersio, J. F., & McCarty, J. M. (2009). Improving stem cell mobilization strategies: future directions. Bone Marrow Transplantation, 43, 181–195.PubMedCrossRefGoogle Scholar
  35. 35.
    Devine, H., Tierney, D. K., Schmit-Pokorny, K., & McDermott, K. (2010). Mobilization of hematopoietic stem cells for use in autologous transplantation. Clinical Journal of Oncology Nursing, 14, 212–222.PubMedCrossRefGoogle Scholar
  36. 36.
    Fruehauf, S., Seeger, T., & Topaly, J. (2005). Innovative strategies for PBPC mobilization. Cytotherapy, 7, 438–446.PubMedCrossRefGoogle Scholar
  37. 37.
    Greinix, H. T., & Worel, N. (2009). New agents for mobilizing peripheral blood stem cells. Transfusion and Apheresis Science, 41, 67–71.PubMedCrossRefGoogle Scholar
  38. 38.
    Jacoub, J. F., Suryadevara, U., Pereyra, V., et al. (2006). Mobilization strategies for the collection of peripheral blood progenitor cells: Results from a pilot study of delayed addition G-CSF following chemotherapy and review of the literature. Experimental Hematology, 34, 1443–1450.PubMedCrossRefGoogle Scholar
  39. 39.
    Moog, R. (2008). Management strategies for poor peripheral blood stem cell mobilization. Transfusion and Apheresis Science, 38, 229–236.PubMedCrossRefGoogle Scholar
  40. 40.
    Pusic, I., & DiPersio, J. F. (2008). The use of growth factors in hematopoietic stem cell transplantation. Current Pharmaceutical Design, 14, 1950–1961.PubMedCrossRefGoogle Scholar
  41. 41.
    Rosenbeck, L. L., Srivastava, S., & Kiel, P. J. (2010). Peripheral blood stem cell mobilization tactics. Annals of Pharmacotherapy, 44, 107–116.PubMedCrossRefGoogle Scholar
  42. 42.
    Vose, J. M., Ho, A. D., Coiffier, B., et al. (2009). Advances in mobilization for the optimization of autologous stem cell transplantation. Leukemia & Lymphoma, 50, 1412–1421.CrossRefGoogle Scholar
  43. 43.
    Perseghin, P., Terruzzi, E., Dassi, M., et al. (2009). Management of poor peripheral blood stem cell mobilization: incidence, predictive factors, alternative strategies and outcome. A retrospective analysis on 2177 patients from three major Italian institutions. Transfusion and Apheresis Science, 41, 33–37.PubMedCrossRefGoogle Scholar
  44. 44.
    Nervi, B., Link, D. C., & DiPersio, J. F. (2006). Cytokines and hematopoietic stem cell mobilization. Journal of Cellular Biochemistry, 99, 690–705.PubMedCrossRefGoogle Scholar
  45. 45.
    Liongue, C., Wright, C., Russell, A. P., & Ward, A. C. (2009). Granulocyte colony-stimulating factor receptor: stimulating granulopoiesis and much more. International Journal of Biochemistry & Cell Biology, 41, 2372–2375.CrossRefGoogle Scholar
  46. 46.
    Liu, F., Poursine-Laurent, J., & Link, D. C. (2000). Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF. Blood, 95, 3025–3031.PubMedGoogle Scholar
  47. 47.
    Pruijt, J. F., Verzaal, P., van Os, R., et al. (2002). Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice. Proceedings of the National Academy of Sciences USA, 99, 6228–6233.CrossRefGoogle Scholar
  48. 48.
    Roberts, A. W., Foote, S., Alexander, W. S., Scott, C., Robb, L., & Metcalf, D. (1997). Genetic influences determining progenitor cell mobilization and leukocytosis induced by granulocyte colony-stimulating factor. Blood, 89, 2736–2744.PubMedGoogle Scholar
  49. 49.
    Janowska-Wieczorek, A., Marquez, L. A., Nabholtz, J. M., et al. (1999). Growth factors and cytokines upregulate gelatinase expression in bone marrow CD34(+) cells and their transmigration through reconstituted basement membrane. Blood, 93, 3379–3390.PubMedGoogle Scholar
  50. 50.
    Levesque, J. P., Hendy, J., Takamatsu, Y., Williams, B., Winkler, I. G., & Simmons, P. J. (2002). Mobilization by either cyclophosphamide or granulocyte colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Experimental Hematology, 30, 440–449.PubMedCrossRefGoogle Scholar
  51. 51.
    Kobbe, G., Bruns, I., Fenk, R., Czibere, A., & Haas, R. (2009). Pegfilgrastim for PBSC mobilization and autologous haematopoietic SCT. Bone Marrow Transplantation, 43, 669–677.PubMedCrossRefGoogle Scholar
  52. 52.
    Yatuv, R., Carmel-Goren, L., Dayan, I., Robinson, M., & Baru, M. (2009). Binding of proteins to PEGylated liposomes and improvement of G-CSF efficacy in mobilization of hematopoietic stem cells. Journal of Controlled Release, 135, 44–50.PubMedCrossRefGoogle Scholar
  53. 53.
    Fukuda, S., Bian, H., King, A. G., & Pelus, L. M. (2007). The chemokine GRObeta mobilizes early hematopoietic stem cells characterized by enhanced homing and engraftment. Blood, 110, 860–869.PubMedCrossRefGoogle Scholar
  54. 54.
    Herbert, K. E., Prince, H. M., Ritchie, D. S., & Seymour, J. F. (2010). The role of ancestim (recombinant human stem-cell factor, rhSCF) in hematopoietic stem cell mobilization and hematopoietic reconstitution. Expert Opinion on Biological Therapy, 10, 113–125.PubMedCrossRefGoogle Scholar
  55. 55.
    de Kruijf, E. J., Hagoort, H., Velders, G. A., Fibbe, W. E., & van Pel, M. (2010). Hematopoietic stem and progenitor cells are differentially mobilized depending on the duration of Flt3-ligand administration. Haematologica, 95, 1061–1067.PubMedCrossRefGoogle Scholar
  56. 56.
    Bertho, J. M., Prat, M., Stefani, J., et al. (2008). Correlation between plasma Flt3-ligand concentration and hematopoiesis during G-CSF-induced CD34+ cell mobilization. Stem Cells and Development, 17, 1221–1225.PubMedCrossRefGoogle Scholar
  57. 57.
    Jalili, A., Shirvaikar, N., Marquez-Curtis, L. A., Turner, A. R., & Janowska-Wieczorek, A. (2009). The HGF/c-Met axis synergizes with G-CSF in the mobilization of hematopoietic stem/progenitor cells. Stem Cells and Development, 19, 1143–1151.CrossRefGoogle Scholar
  58. 58.
    Tesio, M., Golan, K., Corso, S., et al. (2010). Enhanced c-Met activity promotes G-CSF induced mobilization of hematopoietic progenitor cells via ROS signaling. Blood, Jun 28. [Epub ahead of print].Google Scholar
  59. 59.
    Kucia, M., Reca, R., Miekus, K., et al. (2005). Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells, 23, 879–894.PubMedCrossRefGoogle Scholar
  60. 60.
    Christopher, M. J., Liu, F., Hilton, M. J., Long, F., & Link, D. C. (2009). Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization. Blood, 114, 1331–1339.PubMedCrossRefGoogle Scholar
  61. 61.
    Levesque, J. P., Hendy, J., Takamatsu, Y., Simmons, P. J., & Bendall, L. J. (2003). Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. Journal of Clinical Investigation, 111, 187–196.PubMedGoogle Scholar
  62. 62.
    Semerad, C. L., Christopher, M. J., Liu, F., et al. (2005). G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood, 106, 3020–3027.PubMedCrossRefGoogle Scholar
  63. 63.
    Petit, I., Szyper-Kravitz, M., Nagler, A., et al. (2002). G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nature Immunology, 3, 687–694.PubMedCrossRefGoogle Scholar
  64. 64.
    Kim, H. K., De La Luz Sierra, M., Williams, C. K., Gulino, A. V., & Tosato, G. (2006). G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells. Blood, 108, 812–820.PubMedCrossRefGoogle Scholar
  65. 65.
    Crump, M. P., Gong, J. H., Loetscher, P., et al. (1997). Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1. EMBO Journal, 16, 6996–7007.PubMedCrossRefGoogle Scholar
  66. 66.
    Pusic, I., & DiPersio, J. F. (2010). Update on clinical experience with AMD3100, an SDF-1/CXCL12-CXCR4 inhibitor, in mobilization of hematopoietic stem and progenitor cells. Current Opinion in Hematology, 17, 319–326.PubMedCrossRefGoogle Scholar
  67. 67.
    Duarte, R. F., Shaw, B. E., Marín, P., et al. (2010). Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data. Bone Marrow Transplantation, Mar 22 [Epub ahead of print].Google Scholar
  68. 68.
    DiPersio, J. F., Stadtmauer, E. A., Nademanee, A., et al. (2009). Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood, 113, 5720–5726.PubMedGoogle Scholar
  69. 69.
    Bonig, H., Chudziak, D., Priestley, G., & Papayannopoulou, T. (2009). Insights into the biology of mobilized hematopoietic stem/progenitor cells through innovative treatment schedules of the CXCR4 antagonist AMD3100. Experimental Hematology, 37, 402–415.PubMedCrossRefGoogle Scholar
  70. 70.
    McQuibban, G. A., Butler, G. S., Gong, J. H., et al. (2001). Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. Journal of Biological Chemistry, 276, 43503–43508.PubMedCrossRefGoogle Scholar
  71. 71.
    Lambeir, A. M., Proost, P., Durinx, C., et al. (2001). Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family. Journal of Biological Chemistry, 276, 29839–29845.PubMedCrossRefGoogle Scholar
  72. 72.
    Delgado, M. B., Clark-Lewis, I., Loetscher, P., et al. (2001). Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes. European Journal of Immunology, 31, 699–707.PubMedCrossRefGoogle Scholar
  73. 73.
    Valenzuela-Fernandez, A., Planchenault, T., Baleux, F., et al. (2002). Leukocyte elastase negatively regulates stromal cell-derived factor-1 (SDF-1)/CXCR4 binding and functions by amino-terminal processing of SDF-1 and CXCR4. Journal of Biological Chemistry, 277, 15677–15689.PubMedCrossRefGoogle Scholar
  74. 74.
    Kollet, O., Dar, A., Shivtiel, S., et al. (2006). Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nature Medicine, 12, 657–664.PubMedCrossRefGoogle Scholar
  75. 75.
    Velders, G. A., & Fibbe, W. E. (2005). Involvement of proteases in cytokine-induced hematopoietic stem cell mobilization. Annals of the New York Academy of Sciences, 1044, 60–69.PubMedCrossRefGoogle Scholar
  76. 76.
    Davis, D. A., Singer, K. E., De La Luz Sierra, M., et al. (2005). Identification of carboxypeptidase N as an enzyme responsible for C-terminal cleavage of stromal cell-derived factor-1alpha in the circulation. Blood, 105, 4561–4568.PubMedCrossRefGoogle Scholar
  77. 77.
    De La Luz Sierra, M., Yang, F., Narazaki, M., et al. (2004). Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity. Blood, 103, 2452–2459.CrossRefGoogle Scholar
  78. 78.
    Marquez-Curtis, L., Jalili, A., Deiteren, K., Shirvaikar, N., Lambeir, A. M., & Janowska-Wieczorek, A. (2008). Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization? Stem Cells, 26, 1211–1220.PubMedCrossRefGoogle Scholar
  79. 79.
    Levesque, J. P., Liu, F., Simmons, P. J., et al. (2004). Characterization of hematopoietic progenitor mobilization in protease-deficient mice. Blood, 104, 65–72.PubMedCrossRefGoogle Scholar
  80. 80.
    Butler, G. S., & Overall, C. M. (2009). Updated biological roles for matrix metalloproteinases and new “intracellular” substrates revealed by degradomics. Biochemistry, 48, 10830–10845.PubMedCrossRefGoogle Scholar
  81. 81.
    Morrison, C. J., Butler, G. S., Rodriguez, D., & Overall, C. M. (2009). Matrix metalloproteinase proteomics: substrates, targets, and therapy. Current Opinion in Cell Biology, 21, 645–653.PubMedCrossRefGoogle Scholar
  82. 82.
    Nagase, H., Visse, R., & Murphy, G. (2006). Structure and function of matrix metalloproteinases and TIMPs. Cardiovascular Research, 69, 562–573.PubMedCrossRefGoogle Scholar
  83. 83.
    Rodriguez, D., Morrison, C. J., & Overall, C. M. (2010). Matrix metalloproteinases: what do they not do? New substrates and biological roles identified by murine models and proteomics. Biochimica et Biophysica Acta, 1803, 39–54.PubMedCrossRefGoogle Scholar
  84. 84.
    Janowska-Wieczorek, A., Marquez, L. A., Matsuzaki, A., et al. (1999). Expression of matrix metalloproteinases (MMP-2 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in acute myelogenous leukaemia blasts: comparison with normal bone marrow cells. British Journal Haematology, 105, 402–411.CrossRefGoogle Scholar
  85. 85.
    Janowska-Wieczorek, A., Matsuzaki, A., & Marquez, L. A. (2000). The hematopoietic microenvironment: Matrix metalloproteinases in the hematopoietic microenvironment. Hematology, 4, 515–527.PubMedGoogle Scholar
  86. 86.
    Marquez-Curtis, L. A., Dobrowsky, A., Montano, J., et al. (2001). Matrix metalloproteinase and tissue inhibitors of metalloproteinase secretion by haematopoietic and stromal precursors and their production in normal and leukaemic long-term marrow cultures. British Journal Haematology, 115, 595–604.CrossRefGoogle Scholar
  87. 87.
    Majka, M., Janowska-Wieczorek, A., Ratajczak, J., et al. (2001). Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood, 97, 3075–3085.PubMedCrossRefGoogle Scholar
  88. 88.
    Janowska-Wieczorek, A., Marquez, L. A., Dobrowsky, A., Ratajczak, M. Z., & Cabuhat, M. L. (2000). Differential MMP and TIMP production by human marrow and peripheral blood CD34(+) cells in response to chemokines. Experimental Hematology, 28, 1274–1285.PubMedCrossRefGoogle Scholar
  89. 89.
    Barbolina, M. V., & Stack, M. S. (2008). Membrane type 1-matrix metalloproteinase: substrate diversity in pericellular proteolysis. Seminars in Cell and Developmental Biology, 19, 24–33.PubMedCrossRefGoogle Scholar
  90. 90.
    Itoh, Y., & Seiki, M. (2006). MT1-MMP: a potent modifier of pericellular microenvironment. Journal of Cell Physiology, 206, 1–8.CrossRefGoogle Scholar
  91. 91.
    Poincloux, R., Lizarraga, F., & Chavrier, P. (2009). Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. Journal of Cell Science, 122, 3015–3024.PubMedCrossRefGoogle Scholar
  92. 92.
    Son, B. R., Marquez-Curtis, L. A., Kucia, M., et al. (2006). Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells, 24, 1254–1264.PubMedCrossRefGoogle Scholar
  93. 93.
    Shirvaikar, N., Reca, R., Jalili, A., et al. (2008). CFU-megakaryocytic progenitors expanded ex vivo from cord blood maintain their in vitro homing potential and express matrix metalloproteinases. Cytotherapy, 10, 182–192.PubMedCrossRefGoogle Scholar
  94. 94.
    Shirvaikar, N., Marquez-Curtis, L. A., Shaw, A. R., Turner, A. R., & Janowska-Wieczorek, A. (2010). MT1-MMP association with membrane lipid rafts facilitates G-CSF-induced hematopoietic stem/progenitor cell mobilization. Experimental Hematology, 38, 823–835.PubMedCrossRefGoogle Scholar
  95. 95.
    Vagima, Y., Avigdor, A., Goichberg, P., et al. (2009). MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization. Journal of Clinical Investigation, 119, 492–503.PubMedCrossRefGoogle Scholar
  96. 96.
    Christopherson, K. W., 2nd, Cooper, S., & Broxmeyer, H. E. (2003). Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells. Blood, 101, 4680–4686.PubMedCrossRefGoogle Scholar
  97. 97.
    Focosi, D., Kast, R. E., Galimberti, S., & Petrini, M. (2008). Conditioning response to granulocyte colony-stimulating factor via the dipeptidyl peptidase IV-adenosine deaminase complex. Journal of Leukocyte Biology, 84, 331–337.PubMedCrossRefGoogle Scholar
  98. 98.
    Tjwa, M., Janssens, S., & Carmeliet, P. (2008). Plasmin therapy enhances mobilization of HPCs after G-CSF. Blood, 112, 4048–4050.PubMedCrossRefGoogle Scholar
  99. 99.
    Staudt, N. D., Aicher, W. K., Kalbacher, H., et al. (2010). Cathepsin X is secreted by human osteoblasts, digests CXCL-12 and impairs adhesion of hematopoietic stem and progenitor cells to osteoblasts. Haematologica, 95, 1452–1460.PubMedCrossRefGoogle Scholar
  100. 100.
    Lee, H., & Ratajczak, M. Z. (2009). Innate immunity: a key player in the mobilization of hematopoietic stem/progenitor cells. Arch Immunol Ther Exp (Warsz), 57, 269–278.CrossRefGoogle Scholar
  101. 101.
    Sekhsaria, S., Fleisher, T. A., Vowells, S., et al. (1996). Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase–deficient severe combined immunodeficiency disease patients. Blood, 88, 1104–1112.PubMedGoogle Scholar
  102. 102.
    Ratajczak, J., Reca, R., Kucia, M., et al. (2004). Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow. Blood, 103, 2071–2078.PubMedCrossRefGoogle Scholar
  103. 103.
    Reca, R., Cramer, D., Yan, J., et al. (2007). A novel role of complement in mobilization: immunodeficient mice are poor granulocyte-colony stimulating factor mobilizers because they lack complement-activating immunoglobulins. Stem Cells, 25, 3093–3100.PubMedCrossRefGoogle Scholar
  104. 104.
    Jalili, A., Shirvaikar, N., Marquez-Curtis, L., et al. (2010). Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. Experimental Hematology, 38, 321–332.PubMedCrossRefGoogle Scholar
  105. 105.
    Lee, H. M., Wu, W., Wysoczynski, M., et al. (2009). Impaired mobilization of hematopoietic stem/progenitor cells in C5-deficient mice supports the pivotal involvement of innate immunity in this process and reveals novel promobilization effects of granulocytes. Leukemia, 23, 2052–2062.PubMedCrossRefGoogle Scholar
  106. 106.
    Ratajczak, M. Z., Lee, H., Wysoczynski, M., et al. (2010). Novel insight into stem cell mobilization: plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex. Leukemia, 24, 976–985.PubMedCrossRefGoogle Scholar
  107. 107.
    Massberg, S., & von Andrian, U. H. (2009). Novel trafficking routes for hematopoietic stem and progenitor cells. Annals of the New York Academy of Sciences, 1176, 87–93.PubMedCrossRefGoogle Scholar
  108. 108.
    Zhang, Y., Cheng, G., Yang, K., et al. (2009). A novel function of granulocyte colony-stimulating factor in mobilization of human hematopoietic progenitor cells. Immunology and Cell Biology, 87, 428–432.PubMedCrossRefGoogle Scholar
  109. 109.
    Lee, H. M., Wysoczynski, M., Liu, R., et al. (2010). Mobilization studies in complement-deficient mice reveal that optimal AMD3100 mobilization of hematopoietic stem cells depends on complement cascade activation by AMD3100-stimulated granulocytes. Leukemia, 24, 573–582.PubMedCrossRefGoogle Scholar
  110. 110.
    Simmons, P. J., Masinovsky, B., Longenecker, B. M., Berenson, R., Torok-Storb, B., & Gallatin, W. M. (1992). Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood, 80, 388–395.PubMedGoogle Scholar
  111. 111.
    Imai, Y., Shimaoka, M., & Kurokawa, M. (2010). Essential roles of VLA-4 in the hematopoietic system. International Journal of Hematology, 91, 569–575.PubMedCrossRefGoogle Scholar
  112. 112.
    Zohren, F., Toutzaris, D., Klarner, V., Hartung, H. P., Kieseier, B., & Haas, R. (2008). The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans. Blood, 111, 3893–3895.PubMedCrossRefGoogle Scholar
  113. 113.
    Ramirez, P., Rettig, M. P., Uy, G. L., et al. (2009). BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood, 114, 1340–1343.PubMedCrossRefGoogle Scholar
  114. 114.
    Bonig, H., Watts, K. L., Chang, K. H., Kiem, H. P., & Papayannopoulou, T. (2009). Concurrent blockade of alpha4-integrin and CXCR4 in hematopoietic stem/progenitor cell mobilization. Stem Cells, 27, 836–837.PubMedCrossRefGoogle Scholar
  115. 115.
    Mythreye, K., & Blobe, G. C. (2009). Proteoglycan signaling co-receptors: roles in cell adhesion, migration and invasion. Cellular Signalling, 21, 1548–1558.PubMedCrossRefGoogle Scholar
  116. 116.
    Vermeulen, M., Le Pesteur, F., Gagnerault, M. C., Mary, J. Y., Sainteny, F., & Lepault, F. (1998). Role of adhesion molecules in the homing and mobilization of murine hematopoietic stem and progenitor cells. Blood, 92, 894–900.PubMedGoogle Scholar
  117. 117.
    Lee, S., Im, S. A., Yoo, E. S., et al. (2000). Mobilization kinetics of CD34(+) cells in association with modulation of CD44 and CD31 expression during continuous intravenous administration of G-CSF in normal donors. Stem Cells, 18, 281–286.PubMedCrossRefGoogle Scholar
  118. 118.
    Rashidi, N., & Adams, G. B. (2009). The influence of parathyroid hormone on the adult hematopoietic stem cell niche. Current Osteoporosis Reports, 7, 53–57.PubMedCrossRefGoogle Scholar
  119. 119.
    Ballen, K. K., Shpall, E. J., Avigan, D., et al. (2007). Phase I trial of parathyroid hormone to facilitate stem cell mobilization. Biology of Blood and Marrow Transplantation, 13, 838–843.PubMedCrossRefGoogle Scholar
  120. 120.
    Katayama, Y., Battista, M., Kao, W. M., et al. (2006). Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell, 124, 407–421.PubMedCrossRefGoogle Scholar
  121. 121.
    Spiegel, A., Kalinkovich, A., Shivtiel, S., Kollet, O., & Lapidot, T. (2008). Stem cell regulation via dynamic interactions of the nervous and immune systems with the microenvironment. Cell Stem Cell, 3, 484–492.PubMedCrossRefGoogle Scholar
  122. 122.
    Mendez-Ferrer, S., Battista, M., & Frenette, P. S. (2010). Cooperation of beta(2)- and beta(3)-adrenergic receptors in hematopoietic progenitor cell mobilization. Annals of the New York Academy of Sciences, 1192, 139–144.PubMedCrossRefGoogle Scholar
  123. 123.
    Bonig, H., Priestley, G. V., & Papayannopoulou, T. (2006). Hierarchy of molecular-pathway usage in bone marrow homing and its shift by cytokines. Blood, 107, 79–86.PubMedCrossRefGoogle Scholar
  124. 124.
    Chavakis, E., Urbich, C., & Dimmeler, S. (2008). Homing and engraftment of progenitor cells: a prerequisite for cell therapy. Journal of Molecular and Cellular Cardiology, 45, 514–522.PubMedCrossRefGoogle Scholar
  125. 125.
    Chute, J. P. (2006). Stem cell homing. Current Opinion in Hematology, 13, 399–406.PubMedCrossRefGoogle Scholar
  126. 126.
    Laird, D. J., von Andrian, U. H., & Wagers, A. J. (2008). Stem cell trafficking in tissue development, growth, and disease. Cell, 132, 612–630.PubMedCrossRefGoogle Scholar
  127. 127.
    Lapidot, T., Dar, A., & Kollet, O. (2005). How do stem cells find their way home? Blood, 106, 1901–1910.PubMedCrossRefGoogle Scholar
  128. 128.
    Papayannopoulou, T. (2003). Bone marrow homing: the players, the playfield, and their evolving roles. Current Opinion in Hematology, 10, 214–219.PubMedCrossRefGoogle Scholar
  129. 129.
    Papayannopoulou, T., & Craddock, C. (1997). Homing and trafficking of hemopoietic progenitor cells. Acta Haematologica, 97, 97–104.PubMedCrossRefGoogle Scholar
  130. 130.
    Quesenberry, P. J., Colvin, G., & Abedi, M. (2005). Perspective: fundamental and clinical concepts on stem cell homing and engraftment: a journey to niches and beyond. Experimental Hematology, 33, 9–19.PubMedCrossRefGoogle Scholar
  131. 131.
    Weidt, C., Niggemann, B., Kasenda, B., Drell, T. L., Zanker, K. S., & Dittmar, T. (2007). Stem cell migration: a quintessential stepping stone to successful therapy. Current Stem Cell Research & Therapy, 2, 89–103.CrossRefGoogle Scholar
  132. 132.
    Quesenberry, P. J., & Becker, P. S. (1998). Stem cell homing: rolling, crawling, and nesting. Proceedings of the National Academy of Sciences USA, 95, 15155–15157.CrossRefGoogle Scholar
  133. 133.
    Frenette, P. S., Subbarao, S., Mazo, I. B., von Andrian, U. H., & Wagner, D. D. (1998). Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow. Proceedings of the National Academy of Sciences USA, 95, 14423–14428.CrossRefGoogle Scholar
  134. 134.
    Simmons, P. J., Zannettino, A., Gronthos, S., & Leavesley, D. (1994). Potential adhesion mechanisms for localisation of haemopoietic progenitors to bone marrow stroma. Leukemia & Lymphoma, 12, 353–363.CrossRefGoogle Scholar
  135. 135.
    Kim, C. H., & Broxmeyer, H. E. (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, 100–110.PubMedGoogle Scholar
  136. 136.
    Lapidot, T., & Kollet, O. (2002). The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia, 16, 1992–2003.PubMedCrossRefGoogle Scholar
  137. 137.
    Mohle, R., Bautz, F., Rafii, S., Moore, M. A., Brugger, W., & Kanz, L. (1998). The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood, 91, 4523–4530.PubMedGoogle Scholar
  138. 138.
    Berthou, C., Marolleau, J. P., Lafaurie, C., et al. (1995). Granzyme B and perforin lytic proteins are expressed in CD34+ peripheral blood progenitor cells mobilized by chemotherapy and granulocyte colony-stimulating factor. Blood, 86, 3500–3506.PubMedGoogle Scholar
  139. 139.
    Moore, M. A. (2002). Cytokine and chemokine networks influencing stem cell proliferation, differentiation, and marrow homing. Journal of Cell Biochemistry, Suppl, 38, 29–38.CrossRefGoogle Scholar
  140. 140.
    Stein, J., Yaniv, I., & Askenasy, N. (2005). Critical early events in hematopoietic cell seeding and engraftment. Folia Histochemica et Cytobiologica, 43, 191–195.PubMedGoogle Scholar
  141. 141.
    Sackstein, R. (2004). The bone marrow is akin to skin: HCELL and the biology of hematopoietic stem cell homing. Journal of Investigative Dermatology, 122, 1061–1069.PubMedGoogle Scholar
  142. 142.
    Gangenahalli, G. U., Singh, V. K., Verma, Y. K., et al. (2006). Hematopoietic stem cell antigen CD34: role in adhesion or homing. Stem Cells and Development, 15, 305–313.PubMedCrossRefGoogle Scholar
  143. 143.
    Forde, S., Tye, B. J., Newey, S. E., et al. (2007). Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells. Blood, 109, 1825–1833.PubMedCrossRefGoogle Scholar
  144. 144.
    Qian, H., Georges-Labouesse, E., Nystrom, A., et al. (2007). Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells. Blood, 110, 2399–2407.PubMedCrossRefGoogle Scholar
  145. 145.
    Bonig, H., Priestley, G. V., Wohlfahrt, M., Kiem, H. P., & Papayannopoulou, T. (2009). Blockade of alpha6-integrin reveals diversity in homing patterns among human, baboon, and murine cells. Stem Cells and Development, 18, 839–844.PubMedCrossRefGoogle Scholar
  146. 146.
    Tada, T., Inoue, N., Widayati, D. T., & Fukuta, K. (2008). Role of MAdCAM-1 and its ligand on the homing of transplanted hematopoietic cells in irradiated mice. Experimental Animals, 57, 347–356.PubMedCrossRefGoogle Scholar
  147. 147.
    Jung, Y., Wang, J., Song, J., et al. (2007). Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood, 110, 82–90.PubMedCrossRefGoogle Scholar
  148. 148.
    Qian, H., Johansson, S., McCourt, P., Smedsrod, B., & Ekblom, M. (2009). Stabilins are expressed in bone marrow sinusoidal endothelial cells and mediate scavenging and cell adhesive functions. Biochemical and Biophysical Research Communications, 390, 883–886.PubMedCrossRefGoogle Scholar
  149. 149.
    Hosokawa, K., Arai, F., Yoshihara, H., et al. (2010). Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. Blood, 116, 554–563.PubMedCrossRefGoogle Scholar
  150. 150.
    Gomez-Mouton, C., Lacalle, R. A., Mira, E., et al. (2004). Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. Journal of Cell Biology, 164, 759–768.PubMedCrossRefGoogle Scholar
  151. 151.
    Nguyen, D. H., & Taub, D. (2002). CXCR4 function requires membrane cholesterol: implications for HIV infection. Journal of Immunology, 168, 4121–4126.Google Scholar
  152. 152.
    Wysoczynski, M., Reca, R., Ratajczak, J., et al. (2005). Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient. Blood, 105, 40–48.PubMedCrossRefGoogle Scholar
  153. 153.
    Baumert, B., Grymula, K., Pietruszka, D., et al. (2008). An optimization of hematopoietic stem and progenitor cell isolation for scientific and clinical purposes by the application of a new parameter determining the hematopoietic graft efficacy. Folia Histochemica et Cytobiologica, 46, 299–305.PubMedCrossRefGoogle Scholar
  154. 154.
    Fruehauf, S., & Tricot, G. (2010). Comparison of unmobilized and mobilized graft characteristics and the implications of cell subsets on autologous and allogeneic transplant outcomes. Biology of Blood and Marrow Transplantation, 16, 1629–1648.PubMedCrossRefGoogle Scholar
  155. 155.
    Bensinger, W., Appelbaum, F., Rowley, S., et al. (1995). Factors that influence collection and engraftment of autologous peripheral-blood stem cells. Journal of Clinical Oncology, 13, 2547–2555.PubMedGoogle Scholar
  156. 156.
    Klaus, J., Herrmann, D., Breitkreutz, I., et al. (2007). Effect of CD34 cell dose on hematopoietic reconstitution and outcome in 508 patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. European Journal of Haematology, 78, 21–28.PubMedCrossRefGoogle Scholar
  157. 157.
    Tricot, G., Jagannath, S., Vesole, D., et al. (1995). Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood, 85, 588–596.PubMedGoogle Scholar
  158. 158.
    Weaver, C. H., Hazelton, B., Birch, R., et al. (1995). An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood, 86, 3961–3969.PubMedGoogle Scholar
  159. 159.
    Cashen, A. F., Lazarus, H. M., & Devine, S. M. (2007). Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF? Bone Marrow Transplantation, 39, 577–588.PubMedCrossRefGoogle Scholar
  160. 160.
    Oran, B., Malek, K., Sanchorawala, V., et al. (2005). Predictive factors for hematopoietic engraftment after autologous peripheral blood stem cell transplantation for AL amyloidosis. Bone Marrow Transplantation, 35, 567–575.PubMedCrossRefGoogle Scholar
  161. 161.
    Marquez-Curtis, L. A., Turner, A. R., Larratt, L. M., Letcher, B., Lee, S. F., & Janowska-Wieczorek, A. (2009). CD34+ cell responsiveness to stromal-cell derived factor-1alpha underlies rate of engraftment after peripheral blood stem cell transplantation. Transfusion, 49, 161–169.PubMedCrossRefGoogle Scholar
  162. 162.
    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, 2942–2949.PubMedCrossRefGoogle Scholar
  163. 163.
    Cheung, P., Allis, C. D., & Sassone-Corsi, P. (2000). Signaling to chromatin through histone modifications. Cell, 103, 263–271.PubMedCrossRefGoogle Scholar
  164. 164.
    Bug, G., Gul, H., Schwarz, K., et al. (2005). Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Research, 65, 2537–2541.PubMedCrossRefGoogle Scholar
  165. 165.
    Gul, H., Marquez-Curtis, L. A., Jahroudi, N., Lo, J., Turner, A. R., & Janowska-Wieczorek, A. (2009). Valproic acid increases CXCR4 expression in hematopoietic stem/progenitor cells by chromatin remodeling. Stem Cells and Development, 18, 831–838.PubMedCrossRefGoogle Scholar
  166. 166.
    Bonig, H., Priestley, G. V., Oehler, V., & Papayannopoulou, T. (2007). Hematopoietic progenitor cells (HPC) from mobilized peripheral blood display enhanced migration and marrow homing compared to steady-state bone marrow HPC. Experimental Hematology, 35, 326–334.PubMedCrossRefGoogle Scholar
  167. 167.
    Elfenbein, G. J., & Sackstein, R. (2004). Primed marrow for autologous and allogeneic transplantation: a review comparing primed marrow to mobilized blood and steady-state marrow. Experimental Hematology, 32, 327–339.PubMedCrossRefGoogle Scholar
  168. 168.
    Janowska-Wieczorek, A., Majka, M., Kijowski, J., et al. (2001). Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood, 98, 3143–3149.PubMedCrossRefGoogle Scholar
  169. 169.
    Al-Nedawi, K., Meehan, B., & Rak, J. (2009). Microvesicles: messengers and mediators of tumor progression. Cell Cycle, 8, 2014–2018.PubMedCrossRefGoogle Scholar
  170. 170.
    Nomura, S., Ozaki, Y., & Ikeda, Y. (2008). Function and role of microparticles in various clinical settings. Thrombosis Research, 123, 8–23.PubMedCrossRefGoogle Scholar
  171. 171.
    Ratajczak, J., Wysoczynski, M., Hayek, F., Janowska-Wieczorek, A., & Ratajczak, M. Z. (2006). Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia, 20, 1487–1495.PubMedCrossRefGoogle Scholar
  172. 172.
    Simak, J., & Gelderman, M. P. (2006). Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfusion Medicine Reviews, 20, 1–26.PubMedCrossRefGoogle Scholar
  173. 173.
    Baj-Krzyworzeka, M., Majka, M., Pratico, D., et al. (2002). Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Experimental Hematology, 30, 450–459.PubMedCrossRefGoogle Scholar
  174. 174.
    Janowska-Wieczorek, A., Marquez-Curtis, L. A., Wysoczynski, M., & Ratajczak, M. Z. (2006). Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion, 46, 1199–1209.PubMedCrossRefGoogle Scholar
  175. 175.
    Janowska-Wieczorek, A., Wysoczynski, M., Kijowski, J., et al. (2005). Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. International Journal of Cancer, 113, 752–760.CrossRefGoogle Scholar
  176. 176.
    Avigdor, A., Goichberg, P., Shivtiel, S., et al. (2004). CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood, 103, 2981–2989.PubMedCrossRefGoogle Scholar
  177. 177.
    Lane, D. A., Philippou, H., & Huntington, J. A. (2005). Directing thrombin. Blood, 106, 2605–2612.PubMedCrossRefGoogle Scholar
  178. 178.
    Shirvaikar, N., Marquez-Curtis, L. A., Ratajczak, M. Z., Janowska-Wieczorek, A. (2010). Hyaluronic acid and thrombin upregulate MT1-MMP through PI3K and Rac-1 signaling and prime the homing-related responses of cord blood hematopoietic stem/progenitor cells. Stem Cells and Development, Oct 25 [Epub ahead of print].Google Scholar
  179. 179.
    Roy, R., Yang, J., & Moses, M. A. (2009). Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. Journal of Clinical Oncology, 27, 5287–5297.PubMedCrossRefGoogle Scholar
  180. 180.
    Kolsch, V., Charest, P. G., & Firtel, R. A. (2008). The regulation of cell motility and chemotaxis by phospholipid signaling. Journal of Cell Science, 121, 551–559.PubMedCrossRefGoogle Scholar
  181. 181.
    Cancelas, J. A., Jansen, M., & Williams, D. A. (2006). The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilization. Experimental Hematology, 34, 976–985.PubMedCrossRefGoogle Scholar
  182. 182.
    Cancelas, J. A., Lee, A. W., Prabhakar, R., Stringer, K. F., Zheng, Y., & Williams, D. A. (2005). Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nature Medicine, 11, 886–891.PubMedCrossRefGoogle Scholar
  183. 183.
    Etienne-Manneville, S., & Hall, A. (2002). Rho GTPases in cell biology. Nature, 420, 629–635.PubMedCrossRefGoogle Scholar
  184. 184.
    Williams, D. A., Zheng, Y., & Cancelas, J. A. (2008). Rho GTPases and regulation of hematopoietic stem cell localization. Methods in Enzymology, 439, 365–393.PubMedCrossRefGoogle Scholar
  185. 185.
    Charest, P. G., & Firtel, R. A. (2006). Feedback signaling controls leading-edge formation during chemotaxis. Current Opinion in Genetics & Development, 16, 339–347.CrossRefGoogle Scholar
  186. 186.
    Fuhler, G. M., Drayer, A. L., Olthof, S. G., Schuringa, J. J., Coffer, P. J., & Vellenga, E. (2008). Reduced activation of protein kinase B, Rac, and F-actin polymerization contributes to an impairment of stromal cell derived factor-1 induced migration of CD34+ cells from patients with myelodysplasia. Blood, 111, 359–368.PubMedCrossRefGoogle Scholar
  187. 187.
    Campbell, T. B., & Broxmeyer, H. E. (2008). CD26 inhibition and hematopoiesis: a novel approach to enhance transplantation. Frontiers in Bioscience, 13, 1795–1805.PubMedCrossRefGoogle Scholar
  188. 188.
    Tjwa, M., Sidenius, N., Moura, R., et al. (2009). Membrane-anchored uPAR regulates the proliferation, marrow pool size, engraftment, and mobilization of mouse hematopoietic stem/progenitor cells. Journal of Clinical Investigation, 119, 1008–1018.PubMedGoogle Scholar
  189. 189.
    Grundler, R., Brault, L., Gasser, C., et al. (2009). Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration. Journal of Experimental Medicine, 206, 1957–1970.PubMedCrossRefGoogle Scholar
  190. 190.
    Basu, S., Ray, N. T., Atkinson, S. J., & Broxmeyer, H. E. (2007). Protein phosphatase 2A plays an important role in stromal-cell derived factor-1/CXC chemokine ligand 12-mediated migration and adhesion of CD34+ cells. Journal of Immunology, 179, 3075–3085.Google Scholar
  191. 191.
    Sonntag, J., Emeis, M., Vornwald, A., Strauss, E., & Maier, R. F. (1998). Complement activation during plasma production depends on the apheresis technique. Transfusion Medicine, 8, 205–208.PubMedCrossRefGoogle Scholar
  192. 192.
    Reca, R., Mastellos, D., Majka, M., et al. (2003). Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1. Blood, 101, 3784–3793.PubMedCrossRefGoogle Scholar
  193. 193.
    Jalili, A., Marquez-Curtis, L., Shirvaikar, N., Wysoczynski, M., Ratajczak, M. Z., & Janowska-Wieczorek, A. (2010). Complement C1q enhances homing-related responses of hematopoietic stem/progenitor cells. Transfusion, 50, 2002–2010.PubMedCrossRefGoogle Scholar
  194. 194.
    Kang, Y., Chen, B. J., Deoliveira, D., Mito, J., & Chao, N. J. (2010). Selective enhancement of donor hematopoietic cell engraftment by the CXCR4 antagonist AMD3100 in a mouse transplantation model. PLoS One, 5, e11316.PubMedCrossRefGoogle Scholar
  195. 195.
    Hoggatt, J., Singh, P., Sampath, J., & Pelus, L. M. (2009). Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood, 113, 5444–5455.PubMedCrossRefGoogle Scholar
  196. 196.
    Durand, E. M., & Zon, L. I. (2010). Newly emerging roles for prostaglandin E2 regulation of hematopoiesis and hematopoietic stem cell engraftment. Current Opinion in Hematology, 17, 308–312.PubMedCrossRefGoogle Scholar
  197. 197.
    Pelus, L. M., & Fukuda, S. (2008). Chemokine-mobilized adult stem cells: defining a better hematopoietic graft. Leukemia, 22, 466–473.PubMedCrossRefGoogle Scholar
  198. 198.
    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. Journal of Biological Chemistry, 280, 35760–35766.PubMedCrossRefGoogle Scholar
  199. 199.
    Burns, J. M., Summers, B. C., Wang, Y., et al. (2006). A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. Journal of Experimental Medicine, 203, 2201–2213.PubMedCrossRefGoogle Scholar
  200. 200.
    Maksym, R. B., Tarnowski, M., Grymula, K., et al. (2009). The role of stromal-derived factor-1−CXCR7 axis in development and cancer. European Journal of Pharmacology, 625, 31–40.PubMedCrossRefGoogle Scholar
  201. 201.
    Boldajipour, B., Mahabaleshwar, H., Kardash, E., et al. (2008). Control of chemokine-guided cell migration by ligand sequestration. Cell, 132, 463–473.PubMedCrossRefGoogle Scholar
  202. 202.
    Broxmeyer, H. E. (2005). Biology of cord blood cells and future prospects for enhanced clinical benefit. Cytotherapy, 7, 209–218.PubMedCrossRefGoogle Scholar
  203. 203.
    Gluckman, E. (2009). History of cord blood transplantation. Bone Marrow Transplantation, 44, 621–626.PubMedCrossRefGoogle Scholar
  204. 204.
    Stanevsky, A., Goldstein, G., & Nagler, A. (2009). Umbilical cord blood transplantation: pros, cons and beyond. Blood Reviews, 2, 199–204.CrossRefGoogle Scholar
  205. 205.
    Delaney, C., Ratajczak, M. Z., & Laughlin, M. J. (2010). Strategies to enhance umbilical cord blood stem cell engraftment in adult patients. Expert Reviews in Hematology, 3, 273–283.CrossRefGoogle Scholar
  206. 206.
    Stanevsky, A., Shimoni, A., Yerushalmi, R., & Nagler, A. (2010). Cord blood stem cells for hematopoietic transplantation. Stem Cell Reviews and Reports. Sept 1 [Epub ahead of print].Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Leah A. Marquez-Curtis
    • 1
  • A. Robert Turner
    • 2
  • Santhi Sridharan
    • 1
  • Mariusz Z. Ratajczak
    • 3
  • Anna Janowska-Wieczorek
    • 1
    • 2
    Email author
  1. 1.Research & DevelopmentCanadian Blood ServicesEdmontonCanada
  2. 2.Departments of Medicine and OncologyUniversity of AlbertaEdmontonCanada
  3. 3.Stem Cell Biology Program at James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA

Personalised recommendations