Stem Cell Reviews

, 4:137 | Cite as

The Paradoxical Dynamism of Marrow Stem Cells: Considerations of Stem Cells, Niches, and Microvesicles

  • Peter J. QuesenberryEmail author
  • Jason M. Aliotta


Marrow stem cell regulation represents a complex and flexible system. It has been assumed that the system was intrinsically hierarchical in nature, but recent data has indicated that at the progenitor/stem cell level the system may represent a continuum with reversible alterations in phenotype occurring as the stem cells transit cell cycle. Short and long-term engraftment, in vivo and in vitro differentiation, gene expression, and progenitor numbers have all been found to vary reversibly with cell cycle. In essence, the stem cells appear to show variable potential, probably based on transcription factor access, as they proceed through cell cycle. Another critical component of the stem cell regulation is the microenvironment, so-called niches. We propose that there are not just several unique niche cells, but a wide variety of niche cells which continually change phenotype to appropriately interact with the continuum of stem cell phenotypes. A third component of the regulatory system is microvesicle transfer of genetic information between cells. We have shown that marrow cells can express the genetic phenotype of pulmonary epithelial cells after microvesicle transfer from lung to marrow cells. Similar transfers of tissue specific mRNA occur between liver, brain, and heart to marrow cells. Thus, there would appear to be a continuous genetic modulation of cells through microvesicle transfer between cells. We propose that there is an interactive triangulated Venn diagram with continuously changing stem cells interacting with continuously changing areas of influence, both being modulated by transfer of genetic information by microvesicles.


Stem cell Cell cycle Continuum Areas of influence Differentiation Microvesicle Cell communication Lung injury Co-culture Gene expression 



Grant funding has been provided by NCRR, NIDDK, and NHLBI, #P20RR018757, R01DK061858, R01HL073749 and #K08HL086868.


  1. 1.
    Till, J. E., & McCulloch, E. A. (1961). A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiation Research, 14, 213–222.PubMedGoogle Scholar
  2. 2.
    Till, J. E., McCulloch, E. A., & Siminovitch, L. (1964). A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proceedings of the National Academy of Sciences of the United States of America, 51, 29–36.PubMedGoogle Scholar
  3. 3.
    Cronkite, E. P., Bond, V. P., Fleidner, T. M., & Killmann, S. A. (1960). The use of tritiated thymidine in the study of haemopoietic cell proliferation. In G. E. W. Wolstenholme (Ed.), O’Connor’s ciba foundation on haemopoeisis (pp. 70–92). London: J and A Churchill, Ltd.Google Scholar
  4. 4.
    Cronkite, E. P., & Vincent, P. C (1969). Granulocytopoiesis. Ser Haemat, 3–43.Google Scholar
  5. 5.
    Cronkite, E. P., Burlington, H., Chanana, A. D., et al. (1977). Concepts and observations on the regulation of granulopoiesis. In S. J. Baum, & G. D. Ledney (Eds.), Experimental hematology today (pp. 41–48). NY: Springer.Google Scholar
  6. 6.
    Fleidner, T. M., Cronkite, E. P., Killman, S. A., & Bond, V. P. (1964). Granulocytopoiesis II Emergence and pattern of labeling of neutrophilic granulocytes in human beings. Blood, 24, 683–700.Google Scholar
  7. 7.
    Cronkite, E. P. (1975). Hemopoietic stem cells: an analytic review of hemopoiesis. Pathobiology Annual, 5, 35–69.PubMedGoogle Scholar
  8. 8.
    Quesenberry, P. J., Morley, A., Miller, M., Rickard, K., Howard, D., & Stohlman Jr., F. (1973). Effect of endotoxin on granulopoiesis and the in vitro colony-forming cell. Blood, 41(3), 391–398.PubMedGoogle Scholar
  9. 9.
    Bradley, T. R., & Metcalf, D. (1966). The growth of mouse bone marrow cells in vitro. Journal of Experimental Biology and Medical Science, 44, 287–300.Google Scholar
  10. 10.
    Pluznik, D. H., & Sachs, L. (1965). The cloning of normal “mast” cells in tissue culture. Journal of Cellular and Comparative Physiology, 66, 319–324.Google Scholar
  11. 11.
    Axelrad, A. A., McLeod, D. L., Shreeve, M. M. et al. (1973). DHEW Publication 226–234.Google Scholar
  12. 12.
    McLeod, D. L., Shreeve, M. M., & Axelrad, A. A. (1974). Improved plasma culture system for production of erythrocytic colonies in vitro: quantitative assay method for CFU-E. Blood, 44, 517–534.PubMedGoogle Scholar
  13. 13.
    Iscove, N. N., & Siever, F. (1975). Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Experimental Hematology, 3, 32–43.PubMedGoogle Scholar
  14. 14.
    Nakeff, A., Dicke, K. A., & Van Noord, M. J. (1975). Megakaryocytes in agar cultures of mouse bone marrow. Series Haematologica, 8, 4–21.PubMedGoogle Scholar
  15. 15.
    Metcalf, D., MacDonald, H. R., Odartchenko, N., et al. (1975). Growth of mouse megakaryocyte colonies in vitro. Proceedings of the National Academy of Sciences of the United States of America, 72, 1744–1748.PubMedGoogle Scholar
  16. 16.
    Axelrad, A. A., McLeod, D. L., Suzuki, S., Shreeve, M. M. (1978). Cold Spring Harbor Press 155.Google Scholar
  17. 17.
    Gregory, C. J. (1976). Erythropoietin sensitivity as a differentiation marker in the hemopoietic system: studies of three erythropoietic colony responses in culture. Journal of Cellular Physiology, 89, 289.PubMedGoogle Scholar
  18. 18.
    Long, M. W., Gragowski, L. L., Heffner, C. H., & Boxer, L. A. (1986). Phorbol diesters stimulate the development of an early murine progenitor cell. The burst-forming unit-megakaryocyte. Journal of Clinical Investigation, 76, 431–438.Google Scholar
  19. 19.
    Briddell, R. A., Brandt, J. E., Straneva, J. E., Srour, E. F., & Hoffman, R. (1989). Characterization of the human burst forming unit-megakaryocyte. Blood, 74, 145–51.PubMedGoogle Scholar
  20. 20.
    Bertoncello, I., Bartelmez, S. H., Bradley, T. R., et al. (1986). Isolation and analysis of primitive hemopoietic progenitor cells on the basis of differential expression of Qa-m7 antigen. Journal of Immunology, 136, 3219–3224.Google Scholar
  21. 21.
    McNiece, I. K., Stewart, F. M., Deacon, D. H., & Quesenberry, P. J. (1988). Synergistic interactions between hematopoietic growth factors as detected by in vitro mouse bone marrow colony formation. Experimental Hematology, 16, 383–388.PubMedGoogle Scholar
  22. 22.
    McNiece, I. K., Robinson, B. E., & Quesenberry, P. J. (1988). Stimulation of murine colony-forming cells with high proliferative potential by the combination of GM-CSF and CSF-1. Blood, 72, 191–195.PubMedGoogle Scholar
  23. 23.
    McNiece, I. K., Kriegler, A. B., & Quesenberry, P. J. (1989). Studies on the myeloid synergistic factor from 5637: comparison with interleukin-1 alpha. Blood, 73, 919–923.PubMedGoogle Scholar
  24. 24.
    McNiece, I. K., Andrews, R., Stewart, F. M., Clark, S., Boone, T., & Quesenberry, P. J. (1989). Action of IL-3, G-CSF, and GM-CSF on highly enriched human hematopoietic progenitor cells: synergistic interaction of GM-CSF plus G-CSF. Blood, 74, 110–114.PubMedGoogle Scholar
  25. 25.
    McNiece, I. K., Stewart, F. M., Deacon, D. M., et al. (1989). Detection of a human CFC with a high proliferative potential. Blood, 74, 609–612.PubMedGoogle Scholar
  26. 26.
    Kittler, E. L., McGrath, H., Temeles, D., Crittenden, R. B., Kister, V. K., & Quesenberry, P. J. (1992). Biologic significance of constitutive and subliminal growth factor production by bone marrow stroma. Blood, 79, 3168–3178.PubMedGoogle Scholar
  27. 27.
    Lowry, P. A., Deacon, D., Whitefield, P., McGrath, H. E., & Quesenberry, P. J. (1992). Stem Cell Factor induction of in vitro murine hematopoietic colony formation by “subliminal” cytokine combinations: the role of “anchor factors”. Blood, 80, 663–669.PubMedGoogle Scholar
  28. 28.
    Ogawa, M., Pharr, P. N., & Suda, T. (1985). Stochastic nature of stem cell functions in culture pp. 11–19. New York: Alan R. Liss.Google Scholar
  29. 29.
    Nakahata, T., & Ogawa, M. (1982). Hemopoietic colony-forming cells in umbilical cord blood with extensive capability to generate mono- and multipotential hemopoietic progenitors. Journal of Clinical Investigation, 70, 1324–1328.PubMedGoogle Scholar
  30. 30.
    Suda, T., Suda, J., & Ogawa, M. (1984). Disparate differentiation in mouse hemopoietic colonies derived from paired progenitors. Proceedings of the National Academy of Sciences of the United States of America, 81, 2520–2524.PubMedGoogle Scholar
  31. 31.
    Fauser, A. A., & Messner, H. A. (1979). Proliferative state of human pluripotent hemopoietic progenitors (CFUGEMM) in normal individuals and under regenerative conditions after bone marrow transplantation. Blood, 54, 1197–1200.PubMedGoogle Scholar
  32. 32.
    Petzer, A. L., Hogge, D. E., Landsdorp, P. M., Reid, D. S., & Eaves, C. J. (1996). Self-renewal of primitive human hematopoietic cells (long-term-culture-initiating cells) in vitro and their expansion in defined medium. Proceedings of the National Academy of Sciences of the United States of America, 93, 1470–1474.PubMedGoogle Scholar
  33. 33.
    Lemieux, M. E., Revel, V. I., Landsorp, P. M., & Eaves, C. J. (1995). Characterization and purification of a primitive hematopoietic cell type in adult mouse marrow capable of lymphomyeloid differentiation in long term marrow “switch” cultures. Blood, 86, 339–347.Google Scholar
  34. 34.
    Olesen, G., Tender, H., Holm, M. S., & Hokland, P. (2001). Long-term culture of hematopoietic stem cells -validating the stromal component of the CAFC assay. Cytotherapy, 3, 107–116.PubMedGoogle Scholar
  35. 35.
    Forsberg, E. C., Prohaska, S. S., Katzman, S., Heffner, G. C., Stuart, J. M., & Weissman, I. L. (2005). Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genet, 1(3), 328.Google Scholar
  36. 36.
    Rossi, D. J., Bryder, D., Zahn, J. M., et al. (2005). Cell intrinsic alterations underlie hematopoietic stem cell aging. Proceedings of the National Academy of Sciences of the United States of America, 102(26), 9194–9199 June 28.PubMedGoogle Scholar
  37. 37.
    Arber, C., BitMansour, A., Sparer, T. E., et al. (2003). Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation. Blood, 102(2), 421–428 Jul 15.PubMedGoogle Scholar
  38. 38.
    Manz, M. G., Miyamoto, T., Akashi, K., & Weissman, I. L. (2002). Prospective isolation of human clonogenic common myeloid progenitors. Proceedings of the National Academy of Sciences of the United States of America, 99(18), 11872–11877 Sep 3.PubMedGoogle Scholar
  39. 39.
    Miyamoto, T., Iwasaki, H., Reizis, B., et al. (2002). Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Developments of Cell, 3(1), 137–147.Google Scholar
  40. 40.
    Christensen, J. L., & Weissman, I. L. (2001). Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proceedings of the National Academy of Sciences of the United States of America, 98(25), 14541–14546 Dec 4.PubMedGoogle Scholar
  41. 41.
    Kondo, M., Scherer, D. C., King, A. G., Manz, M. G., & Weissman, I. L. (2001). Lymphocyte development from hematopoietic stem cells. Current Opinion in Genetics & Development, 11(5), 520–526.Google Scholar
  42. 42.
    Kondo, M., Scherer, D. C., Miyamoto, T., et al. (2000). Cell fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature, 407(6802), 383–386 Sep 21.PubMedGoogle Scholar
  43. 43.
    Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000). A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature, 404(6774), 193–197 Mar 9.PubMedGoogle Scholar
  44. 44.
    Cheshier, S. H., Morrison, S. J., Liao, X., & Weissman, I. L. (1999). In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 96(6), 3120–3125 Mar 16.PubMedGoogle Scholar
  45. 45.
    Kondo, M., Weissman, I. L., & Akashi, K. (1997). Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell, 91(5), 661–672 Nov 28.PubMedGoogle Scholar
  46. 46.
    Morrison, S. J., Wandycz, A. M., Hemmati, H. D., Wright, D. E., & Weissman, I. L. (1997). Identification of lineage of multipotent hematopoietic progenitors. Development, 124(10), 1929–1939 May.PubMedGoogle Scholar
  47. 47.
    Adolfsson, J., Mansson, R., Buza-Vidas, N., et al. (2005). Identification of Flt3+lympho-myeloid stem cells lacking erythro-megakaryocytic potential: a revised road map for adult blood lineage commitment. Cell, 121, 295–306.PubMedGoogle Scholar
  48. 48.
    Randal, T. D., Lund, F. E., Howard, M. D., & Weissman, I. L. (1996). Expression of murine CD38 defines a population of long-term reconstituting hematopoietic stem cells. Blood, 15, 87(10), 4057–4067 May.Google Scholar
  49. 49.
    Morrison, S. J., & Weissman, I. L. (1994). The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity, 1(8), 661–673 Nov.PubMedGoogle Scholar
  50. 50.
    Forsberg, E. C., Bhattacharya, D., & Weissman, I. L. (2006). Hematopoietic stem cells: expression profiling and beyond. Stem Cell Review, 2(1), 23–30.Google Scholar
  51. 51.
    Warren, L., Bryder, D., Weissman, I. L., & Quake, S. R. (2006). Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR. Proceedings of the National Academy of Sciences of the United States of America, 103(47), 17807–17812 Nov 21.PubMedGoogle Scholar
  52. 52.
    Bryder, D., Rossi, D. J., & Weissman, I. L. (2006). Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. American Journal of Pathology, 169(2), 338–346 Erratum in American Journal of Pathology 2006 Nov;169(5), 1899. Aug.PubMedGoogle Scholar
  53. 53.
    Forsberg, E. C., Serwold, T., Kogan, S., Weissman, I. L., & Passegue, E. (2006). New evidence supporting megakaryocyte-erythrocyte potential of flk2/flt3+ multipotent hematopoietic progenitors. Cell, 126(2), 415–426 Jul 28.PubMedGoogle Scholar
  54. 54.
    Passegue, E., Wagers, A. J., Giuriato, S., Anderson, W. C., & Weissman, I. L. (2005). Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. Journal of Experimental Medicine, 202(11), 1599–1611 Dec 5.PubMedGoogle Scholar
  55. 55.
    Wagers, A. J., & Weissman, I. L. (2006). Differential expression of alpha2 integrin separates long-term and short-term reconstituting Lin-/loThy1.1(lo)c-kit+Sca-1-hematopoietic stem cells. Stem Cells, 24, 1087–1094.PubMedGoogle Scholar
  56. 56.
    Lambert, J. F., Liu, M., Colvin, G. A., et al. (2003). Marrow stem cells shift gene expression and engraftment phenotype with cell cycle transit. Journal of Experimental Medicine, 197(11), 1563–1572.PubMedGoogle Scholar
  57. 57.
    Dooner, G. J., Colvin, G. A., Dooner, M. S., Johnson, K. W., & Quesenberry, P. J. (2008). Gene expression fluctuations in murine hematopoietic stem cells with cell cycle progression. Journal of Cellular Physiology, 214, 786–795.PubMedGoogle Scholar
  58. 58.
    Adolfsson, J., Mansson, R., Buza-Vidas, N., et al. (2002). Identification of flt3 lympho-myeloid stem cells lacking erythro-megakaryocytic potential: a revised road map for adult blood lineage commitment. Cell, 121, 295–306.Google Scholar
  59. 59.
    Lai, A. Y., Lin, S. M., & Kondo, M. (2005). Heterogeneity of Flt3 expressing multipotent progenitors in mouse bone marrow. Journal of Immunology, 175, 5016–5023.Google Scholar
  60. 60.
    Chen, C. -Z., Li, L., Li, M., & Lodish, H. F. (2003). The endoglinpositive rhodaminelow phenotype defines a near-homogeneous population of long-term repopulating hematopoietic stem cells. Immunity, 19, 525–533.PubMedGoogle Scholar
  61. 61.
    Bertoncello, I., Bradley, T. R., Hodgson, G. S., & Dunlop, J. M. (1991). The resolution, enrichment and organization of normal bone marrow high proliferative potential colony-forming cell subsets on the basis of rhodamine-123 fluorescence. Experimental Hematology, 19, 174–178.PubMedGoogle Scholar
  62. 62.
    Zijlmans, J. M., Visser, J. W., Laterveer, L., et al. (1998). The early phase of engraftment after murine blood cell transplantation is mediated by hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 95, 725–729.PubMedGoogle Scholar
  63. 63.
    Wolf, N. S., Kone, A., Priestley, G. V., & Bartelmez, S. H. (1993). In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 3342-rhodamine 123 FACS selection. Experimental Hematology, 21, 614–622.PubMedGoogle Scholar
  64. 64.
    Takano, H., Ema, H., Sudo, K., & Nakauchi, H. (2004). Aymmetric division and lineage commitment at the level of hematopoietic stem cells: inference from differentiation in daughter cells and granddaughter cell pairs. Journal of Experimental Medicine, 199, 295–302.PubMedGoogle Scholar
  65. 65.
    Sieburg, H., Cho, R., Dykstra, B., Uchida, N., Eaves, C., & Muller-Sieburg, C. (2006). Response: discrete stem cell subsets. Blood, 108, 3950.Google Scholar
  66. 66.
    Sieburg, H. B., Cho, R. H., Dykstra, B., Uchida, N., Eaves, C., & Muller-Sieburg, C. E. (2006). The hematopoietic stem cell compartment consists of a limited number of discrete stem cell subsets. Blood, 107, 2311–2316.PubMedGoogle Scholar
  67. 67.
    Kirkland, M. A., Quesenberry, P. J., & Roeder, I. (2006). Discrete stem cells: subsets or a continuum? Blood, 108, 3949.PubMedGoogle Scholar
  68. 68.
    Habibian, H. K., Peters, S. O., Hsieh, C. C., et al. (1998). The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit. Journal of Experimental Medicine, 188(2), 393–398.PubMedGoogle Scholar
  69. 69.
    Cerny, J., Dooner, M., McAuliffe, C., et al. (2002). Homing of purified murine lymphohematopoietic stem cells: a cytokine-induced defect. Journal of Hematotherapy and Stem Cell Research, 11(6), 913–922.PubMedGoogle Scholar
  70. 70.
    Colvin, G. A., Dooner, M. S., Dooner, G. J., et al. (2007). Stem cell continuum: directed differentiation hotspots. Experimental Hematology, 35, 96–107.PubMedGoogle Scholar
  71. 71.
    Colvin, G. A., Lambert, J. F., Carlson, J. E., McAuliffe, C. I., Abedi, M., & Quesenberry, P. J. (2002). Rhythmicity of engraftment and altered cell cycle kinetics of cytokine-cultured murine marrow in simulated microgravity compared with static cultures. In Vitro Cellular & Developmental Biology Animal, 38(6), 343–351.Google Scholar
  72. 72.
    Colvin, G. A., Lambert, J. F., Moore, B. E., et al. (2004). Intrinsic hematopoietic stem cell/progenitor plasticity: inversions. Journal of Cellular Physiology, 199, 20–31.PubMedGoogle Scholar
  73. 73.
    Reddy, G. P., Tiarks, C. Y., Pang, L., Wuu, J., Hsieh, C. C., & Quesenberry, P. J. (1997). Cell cycle analysis and synchronization of pluripotent hematopoietic progenitor stem cells. Blood, 90(6), 2293–2299.PubMedGoogle Scholar
  74. 74.
    Pang, L., Reddy, P. V., McAuliffe, C. I., Colvin, G. A., & Quesenberry, P. J. (2003). Studies on BrdU labeling of hematopoietic cells: stem cells and cell lines. Journal of Cellular Physiology, 197(2), 251–260.PubMedGoogle Scholar
  75. 75.
    Bradford, G. B., Williams, B., Rossi, R., & Bertoncello, I. (1997). Quiescence, cycling, and turn over in the primitive hematopoietic stem cell compartment. Experimental Hematology, 25, 445–453.PubMedGoogle Scholar
  76. 76.
    Fleming, W. H., Alpern, E. J., Uchida, N., Ikuta, K., Spangrude, G. J., & Weissman, I. L. (1993). Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. Journal of Cell Biology, 122, 897–902.PubMedGoogle Scholar
  77. 77.
    Calvi, L. M., Adams, G. B., Welbrecht, K. W., et al. (2003). Osteoblastic cells regulate the hematopoietic niche. Nature, 425, 841–846.PubMedGoogle Scholar
  78. 78.
    Adams, G. B., Chabner, K. T., Alley, I. R., et al. (2006). Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature, 439, 599–603.PubMedGoogle Scholar
  79. 79.
    Koop, H. -G., Avecilla, A. T., Hooper, A. T., & Rafii, S. (2005). The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology, 20, 349–356.Google Scholar
  80. 80.
    Weiss, L. (1976). The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anatomical Record, 186, 161–184.PubMedGoogle Scholar
  81. 81.
    Manwani, D., & Bieker, J. J. (2008). The erythroblastic island. Current Topics in Developmental Biology, 82, 23–53.PubMedCrossRefGoogle Scholar
  82. 82.
    Allen, T. D., & Testa, N. G. (1991). Cellular interactions in erythroblastic islands in long-term bone marrow cultures as studied by time lapse video. Blood Cells, 17, 29–38.PubMedGoogle Scholar
  83. 83.
    Song, Z. X., & Quesenberry, P. J. (1984). Radioresistant murine marrow stromal cells: a morphologic and functional characterization. Experimental Hematology, 12, 523–533.PubMedGoogle Scholar
  84. 84.
    Nilsson, S. K., Dooner, M. S., Tiarks, C. Y., Weier, H. U., & Quesenberry, P. J. (1997). Potential and distribution of transplanted hematopoietic stem cells in a nonablated mouse model. Blood, 89, 4013–4020.PubMedGoogle Scholar
  85. 85.
    Gong, J. K. (1978). Endosteal marrow: a rich source of hematopoietic stem cells. Science, 199, 1443–1445.PubMedGoogle Scholar
  86. 86.
    Taichman, R. S., Reilly, M. J., & Emerson, S. G. (2000). The hematopoietic microenvironment: osteoblasts and the hematopoietic microenvironment. Hematology, 4, 421–426.PubMedGoogle Scholar
  87. 87.
    Dar, A., Kollet, O., & Lapidot, T. (2006). Mutual reciprocal SDF-1/CXCR4 interactions between hematopoietic and bone marrow stromal cells regulate human stem cell migration and development in NOD/SCID chimeric mice. Experimental Hematology, 34, 967–975.PubMedGoogle Scholar
  88. 88.
    Parmar, K., Mauch, P., Vergilio, J. -A., Sackstein, R., & Down, J. D. (2007). Distribution of hematopoetic stem cells in the bone marrow according to regional hypoxia. Proceedings of the National Academy of Sciences, 104, 5431–5436.Google Scholar
  89. 89.
    Jang, Y. -Y., & Sharkis, S. J. (2007). A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low oxygen niche. Blood, 110, 3056–3063.PubMedGoogle Scholar
  90. 90.
    Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126, 677–689.PubMedGoogle Scholar
  91. 91.
    Schofield, R. (1978). The relationship between the spleen colony-forming cell and the Haemopoietic stem cell. Blood Cells, 4, 7–25.PubMedGoogle Scholar
  92. 92.
    Colvin, G. A., Lambert, J. F., Abedi, M., et al. (2004). Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology. Leukemia, 18, 575–583.PubMedGoogle Scholar
  93. 93.
    Hendrikx, P. J., Martens, C. M., Hasgenbeek, A., Keij, J. F., & Visser, J. W. (1996). Homing of fluorescently labeled murine hematopoietic stem cells. Experimental Hematology, 24, 129–140.PubMedGoogle Scholar
  94. 94.
    Quesenberry, P. J., Dooner, G., Dooner, M., & Abedi, M. (2005). Developmental biology: Ignoratio Elenchi: red herrings in stem cell research. Science, 308(5725), 1121–1122.PubMedGoogle Scholar
  95. 95.
    Aliotta, J. M., Keaney, P., Passero, M., et al. (2006). Bone marrow production of lung cells: the impact of G-CSF, cardiotoxin, graded doses of irradiation and subpopulation phenotype. Experimental Hematology, 34, 230–241.PubMedGoogle Scholar
  96. 96.
    Theise, N. D., Henegariu, O., Grove, J., et al. (2002). Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow. Experimental Hematology, 30, 1333–1338.PubMedGoogle Scholar
  97. 97.
    Herzog, E. J., Van Arnam, J., Hu, B., et al. (2006). Threshold of lung injury required for the appearance of marrow-derived lung epithelia. Stem Cells, 24, 1986–1992.PubMedGoogle Scholar
  98. 98.
    Abe, S., Lauby, G., Boyer, C., et al. (2003). Transplanted BM and BM side population cells contribute progeny to the lung and liver in irradiated mice. Cytotherapy, 5, 623–633.Google Scholar
  99. 99.
    Grove, J. E., Lutzko, C., Priller, J., et al. (2002). Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium. American Journal of Respiratory Cell and Molecular Biology, 27, 645–651.PubMedGoogle Scholar
  100. 100.
    Ortiz, L. A., Gambelli, F., & McBride, C. (2003). Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proceedings of the National Academy of Sciences of the United States of America, 100, 8407–8411.PubMedGoogle Scholar
  101. 101.
    Kotton, D. N., Ma, B. Y., Cardoso, W. V., et al. (2001). Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development, 128, 5181–5188.PubMedGoogle Scholar
  102. 102.
    Hashimoto, N., Jin, H., & Liu, T. (2004). Bone marrow-derived progenitor cells in pulmonary fibrosis. Journal of Clinical Investigation, 113, 243–252.PubMedGoogle Scholar
  103. 103.
    Ishizawa, K., Kubo, H., Yamada, M., et al. (2004). Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Letters, 566, 249–252.Google Scholar
  104. 104.
    Baber, S. R., Deng, W., Master, R. G., et al. (2006). Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. American Journal of Physiology, Heart and Circulatory Physiology, 291, H1378–H1383.Google Scholar
  105. 105.
    Beckett, T., Loi, R., Prenovitz, P., et al. (2005). Acute lung injury with endotoxin or NO2 does not enhance development of airway epithelium from bone marrow. Molecular Therapy, 12, 680–686.PubMedGoogle Scholar
  106. 106.
    Loi, R., Beckett, T., Goncz, K. K., et al. (2006). Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells. American Journal of Respiratory and Critical Care Medicine, 173, 171–179.PubMedGoogle Scholar
  107. 107.
    Jiang, Y., Jahagirdar, J. N., Reinhardt, R. L., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41–49.PubMedGoogle Scholar
  108. 108.
    Adachi, Y., Oyaizu, H., Taketani, S., et al. (2004). Treatment and transfer of emphysema by a new bone marrow transplantation method from normal mice to Tsk mice and vice versa. Stem Cells, 24, 2071–2077.Google Scholar
  109. 109.
    Abe, S., Boyer, C., Liu, X., et al. (2004). Cells derived from the circulation contribute to the repair of lung injury. American Journal of Respiratory and Critical Care Medicine, 170, 1158–1163.PubMedGoogle Scholar
  110. 110.
    Bruscia, E. M., Ziegler, E. C., Price, J. E., et al. (2006). Engraftment of donor-derived epithelial cells in multiple organs following bone marrow transplantation into newborn mice. Stem Cells, 24, 2299–2308.PubMedGoogle Scholar
  111. 111.
    Krause, D. S., Theise, N. D., Collector, M. I., et al. (2001). Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 105, 369–377.PubMedGoogle Scholar
  112. 112.
    Macpherson, H., Keir, P., Webb, S., et al. (2005). Bone marrow-derived SP cells can contribute to the respiratory tract of mice in vivo. Journal of Cell Science, 118, 2441–2450.PubMedGoogle Scholar
  113. 113.
    Dooner, M., Cerny, J., Colvin, G., et al. (2004). Homing and conversion of murine hematopoietic stem cells to lung. Blood Cells, Molecules & Diseases, 32, 47–51.Google Scholar
  114. 114.
    Morel, O., Toti, F., Hugel, B., & Freyssinet, J. M. (2004). Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Current Opinion in Hematology, 11, 156–164.PubMedGoogle Scholar
  115. 115.
    Heijnen, H. F., Schiel, A. E., Fijnheer, R., Geuze, H. J., & Sixma, J. J. (1999). Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha granules. Blood, 94, 3791–3799.PubMedGoogle Scholar
  116. 116.
    Nomura, S., Nakamura, T., Cone, J., Tandon, N. N., & Kambayashi, J. (2000). Cytometric analysis of high shear-induced platelet microparticles and effect of cytokines on microparticle generation. Cytometry, 40, 173–181.PubMedGoogle Scholar
  117. 117.
    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.PubMedGoogle Scholar
  118. 118.
    Baj-Krzyworzaka, 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.Google Scholar
  119. 119.
    Rozmyslowicz, T., Majka, M., Kijowski, J., et al. (2003). Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS, 17(1), 33–42 Jan 3.PubMedGoogle Scholar
  120. 120.
    Graves, L. E., Ariztia, E. V., Navari, J. R., Matzel, H. J., Stack, M. S., & Fishman, D. A. (2004). Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Research, 64, 7045–7049.PubMedGoogle Scholar
  121. 121.
    Fackler, O. T., & Peterlin, B. M. (2000). Endocytic entry of HIV-1. Current Biology, 10, 1005–1008.PubMedGoogle Scholar
  122. 122.
    Fevrier, B., Vilette, D., Archer, F., et al. (2004). Cells release prions in association with exosomes. Proceedings of the National Academy of Sciences of the United States of America, 100, 10592–10597.Google Scholar
  123. 123.
    Greco, V., Hannus, M., & Eaton, S. (2001). Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell, 106, 633–645.PubMedGoogle Scholar
  124. 124.
    Speck, R. F., Esser, U., Penn, M. L., et al. (1999). A trans-receptor mechanism for infection of CD4-negative cells by human immunodeficiency virus type 1. Current Biology, 9(10), 547–550 May 20.PubMedGoogle Scholar
  125. 125.
    Ratajczak, J., Miekus, K., Kucia, M., et al. (2006). Embryonic stem cell-derived microvesicles reprogram hematopoietic stem/progenitor cells: evidence for horizontal transfer of mRNA and protein delivery. Leukemia, 20(5), 847–856 May.PubMedGoogle Scholar
  126. 126.
    Baj-Krzyworzaka, M., Szatanek, R., Weglarczyk, K., et al. (2006). Tumor-derived microvesicles carry several surface determinants and mRNA of tumor cells and transfer some of these determinants to monocytes. Cancer Immunology and Immunotherapy, 55, 808–818.Google Scholar
  127. 127.
    Holmgren, L., Szeles, A., Rajnavolgyi, E., et al. (1999). Horizontal transfer of DNA by the uptake of apoptotic bodies. Blood, 93, 3956–3963.PubMedGoogle Scholar
  128. 128.
    Hakelien, A. M., Landsverk, H. B., Rob, J. M., Skalhegg, B. S., & Collas, P. (2002). Reprogramming fibroblasts to express T-cell functions using cell extracts. Nature Biotechnology, 20, 460–466.PubMedGoogle Scholar
  129. 129.
    Deregibus, M. C., Cantaluppi, V., Calogero, R., et al. (2007). Endothelial progenitor cell-derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood, 110(7), 2440–2448 Oct 1.PubMedGoogle Scholar
  130. 130.
    Jin, M., Drwal, G., Bourgeois, T., Saltz, G., & Wu, H. M. (2005). Distinct proteome features of plasma microparticles. Proteomics, 5(1940), 1952.Google Scholar
  131. 131.
    Banfi, C., Brioschi, M., Wait, R., et al. (2005). Proteome of endothelial cell-derived procoagulant microparticles. Proteomics, 5, 4443–4455.PubMedGoogle Scholar
  132. 132.
    Miguet, L., Pacaud, K., Felden, C., et al. (2006). Proteomic analysis of malignant lymphocyte membrane microparticles using double ionization coverage optimization. Proteomics, 6, 153–171.PubMedGoogle Scholar
  133. 133.
    Garcia, B. A., Smalley, D. M., Cho, H., & Shabanowitz, J. (2005). The platelet microparticle proteome. Journal of Proteomics Research, 4, 1516–1521.Google Scholar
  134. 134.
    Choi, D., Lee, J., Park, G. W., et al. (2007). Proteomic analysis of microvesicles derived from human colorectal cancer cells. Journal of Proteomics Research, 6, 4646–4655.Google Scholar
  135. 135.
    Bagnato, C., Thumar, J., Mayya, V., et al. (2007). Proteomic analysis of human coronary atherosclerotic plaque. Molecular Cell Proteomics, 6, 1088–1102.Google Scholar
  136. 136.
    Cho, H. -J., Smalley, D. M., Theodorescu, D., Ley, K., & Lee, J. K. (2007). Statistical identification of differentially labeled peptides from liquid chromatography tandem mass spectrometry. Proteomics, 7, 3681–3692.PubMedGoogle Scholar
  137. 137.
    Jang, Y. Y., Collectopr, M. I., Baylin, S. B., Diehl, A. M., & Sharkis, S. J. (2004). Hematopoietic stem cells convert into liver cells within days without fusion. Nature Cell Biology, 6, 532–539.PubMedGoogle Scholar
  138. 138.
    Aliotta, J. M., Sanchez-Guijo, F. M., Dooner, G. J., et al. (2007). Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation. Stem Cells, 25, 2245–2256.PubMedGoogle Scholar
  139. 139.
    Peters, S. O., Kittler, E. L., Ramshaw, H. S., & Quesenberry, P. J. (1995). Murine marrow cells expanded in culture with IL-3, IL-6, IL-11, and SCF acquire an engraftment defect in normal hosts. Experimental Hematology, 23(5), 461–469.PubMedGoogle Scholar
  140. 140.
    Peters, S. O., Kittler, E. L., Ramshaw, H. S., & Quesenberry, P. J. (1996). Ex vivo expansion of murine marrow cells with interleukin-3 (IL-3), IL-6, IL-11, and stem cell factor leads to impaired engraftment in irradiated hosts. Blood, 87(1), 30–37.PubMedGoogle Scholar
  141. 141.
    Becker, P. S., Nilsson, S. K., Li, Z., et al. (1999). Adhesion receptor expression by hematopoietic cell lines and murine progenitors: modulation by cytokines and cell cycle status. Experimental Hematology, 27(3), 533–541.PubMedGoogle Scholar
  142. 142.
    Berrios, V. M., Dooner, G. J., Nowakowski, G., et al. (2001). The molecular basis for the cytokine-induced defect in homing and engraftment of hematopoietic stem cells. Experimental Hematology, 29(11), 1326–1335.PubMedGoogle Scholar
  143. 143.
    Reddy, G. P., McAuliffe, C. I., Pang, L., Quesenberry, P. J., & Bertoncello, I. (2002). Cytokine receptor repertoire and cytokine responsiveness of Ho dull/Rh dull stem cells with differing potentials for G1/S phase progression. Experimental Hematology, 30(7), 792–800.PubMedGoogle Scholar

Copyright information

© Humana Press 2008

Authors and Affiliations

  1. 1.Department of MedicineThe Warren Alpert Medical School of Brown UniversityProvidenceUSA

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