Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Murine Models

Kinetics of in vivo homing and recruitment into cycle of hematopoietic cells are organ-specific but CD44-independent

Bone Marrow Transplantation volume 26, pages 559–566 (2000)Cite this article

Abstract

In this study, we investigated the homing and initiation of division of fluorescently labelled adult mouse bone marrow cells after their intravenous injection into lethally irradiated congenic mice. After 2 h, only 3% of the transplanted cells remained in the blood, and ∼35% could be retrieved from the marrow, liver and spleen in approximately equal numbers. Subsequently, the proportion of injected cells found in blood, liver and spleen decreased further, but increased slightly (to ∼17%) in the marrow. Homing of progenitors followed a similar pattern. At 22 h post transplant, almost half of the injected cells in the blood, liver and spleen had completed a first mitosis; although these did not include progenitors with in vitro clonogenic ability. at the same time, >90% of the injected cells recovered from the marrow had not yet divided. Parallel studies with CD44−/− mice showed these to contain a numerically and functionally normal stem cell population whose homing and activation in either CD44+/+ or CD44−/− hosts appeared unaltered. These results indicate homing mechanisms that favor more stable retention of transplanted marrow cells in the marrow of the recipient, more rapid activation of some of those cells that home to other sites, and a lack of change in either of these responses when either the transplanted or the recipient cells do not express CD44. Bone Marrow Transplantation (2000) 26, 559–566.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Verfaillie C, Hurley R, Bhatia R, McCarthy JB . Role of bone marrow matrix in normal and abnormal hematopoiesis Crit Rev Oncol Hematol 1994 16: 201–224

    Article  CAS  PubMed  Google Scholar 

  2. Oostendorp RAJ, Reisbach G, Spitzer E et al. VLA-4 and VCAM-1 are the principal adhesion molecules involved in the interaction between blast colony-forming cells and bone marrow stromal cells Br J Haematol 1995 91: 275–284

    Article  CAS  PubMed  Google Scholar 

  3. Levesque JP, Leavesley DI, Niutta S et al. Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins J Exp Med 1995 181: 1805–1815

    Article  CAS  PubMed  Google Scholar 

  4. Legras S, Levesque J-P, Charrad R et al. CD44-mediated adhesiveness of human hematopoietic progenitors to hyluronan is modulated by cytokines Blood 1997 89: 1905–1914

    CAS  PubMed  Google Scholar 

  5. Oostendorp RAJ, Spitzer E, Reisbach G, Dormer P . Antibodies to the β1-integrin chain, CD44, or ICAM-3 stimulate adhesion of blast colony-forming cells and may inhibit their growth Exp Hematol 1997 25: 345–349

    CAS  PubMed  Google Scholar 

  6. Oostendorp RAJ, Spitzer E, Brandl M et al. Evidence for differences in the mechanisms by which antibodies against CD44 promote adhesion of erythroid and granulopoietic progenitors to marrow stromal cells Br J Haematol 1998 101: 436–445

    Article  CAS  PubMed  Google Scholar 

  7. Siminovitch L, McCulloch EA, Till JE . The distribution of colony-forming cells among spleen colonies J Cell Physiol 1963 62: 327–336

    Article  CAS  Google Scholar 

  8. Testa NG, Lord BI, Shore NA . The in vivo seeding of hemopoietic colony-forming cells in irradiated mice Blood 1972 40: 654–661

    CAS  PubMed  Google Scholar 

  9. Lahiri SK, Keizer HJ, Van Putten LM . The efficiency of the assay for haemopoietic colony forming cells Cell Tissue Kinet 1970 3: 355–362

    CAS  PubMed  Google Scholar 

  10. Szilvassy SJ, Bass MJ, Van Zant G, Grimes B . Organ-selective homing defines engraftment kinetics of murine hematopoietic stem cells and is compromised by ex vivo expansion Blood 1999 93: 1557–1566

    CAS  PubMed  Google Scholar 

  11. Williams DA, Rios M, Stephens C, Patel VP . Fibronectin and VLA-4 in haematopoietic stem cell–microenvironment interactions Nature 1991 352: 438–441

    Article  CAS  PubMed  Google Scholar 

  12. Craddock CF, Nakamoto B, Elices M, Papayannopoulou T . The role of CS1 moiety of fibronectin in VLA4-mediated haemopoietic progenitor trafficking Br J Haematol 1997 97: 15–21

    Article  CAS  PubMed  Google Scholar 

  13. Frenette PS, Subbarao S, Mazo IB et al. Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow Proc Natl Acad Sci USA 1998 95: 14423–14428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Broudy VC, Lin NL, Priestley GV et al. Interaction of stem cell factor and its receptor c-kit mediates lodgment and acute expansion of hematopoietic cells in the murine spleen Blood 1996 88: 75–81

    CAS  PubMed  Google Scholar 

  15. Papayannopoulou T, Priestley GV, Nakamoto B . Anti-VLA4/VCAM-1-induced mobilization requires cooperative signaling through the kit/mkit ligand Blood 1998 91: 2231–2239

    CAS  PubMed  Google Scholar 

  16. Ghaffari S, Smadja-Joffe F, Oostendorp R et al. CD44 isoforms in normal and leukemic hematopoiesis Exp Hematol 1999 27: 978–993

    Article  CAS  PubMed  Google Scholar 

  17. Vermeulen M, Le Pesteur F, Gagnerault M-C et al. Role of adhesion molecules in the homing and mobilization of murine hematopoietic stem and progenitor cells Blood 1998 92: 894–900

    CAS  PubMed  Google Scholar 

  18. Khaldoyanidi S, Denzel A, Zöller M . Requirement for CD44 in proliferation and homing of hematopoietic precursors J Leuk Biol 1996 60: 579–592

    Article  CAS  Google Scholar 

  19. Waldman H . Manipulation of T-cell responses with monoclonal antibodies Annu Rev Immunol 1989 7: 407–444

    Article  Google Scholar 

  20. Ghaffari S, Dougherty GJ, Eaves AC, Eaves CJ . Diverse effects of anti-CD44 antibodies on the stromal cell-mediated support of normal but not leukaemic (CML) haemopoiesis in vitro Br J Haematol 1997 97: 22–28

    Article  CAS  PubMed  Google Scholar 

  21. Sandmaier BM, Storb R, Bennett KL et al. Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model Blood 1998 91: 3494–3502

    CAS  PubMed  Google Scholar 

  22. Charrad R-S, Li Y, Delpech B et al. Ligation of the CD44 adhesion molecule reverses blockage of differentiation in human acute myeloid leukemia Nature Med 1999 5: 669–676

    Article  CAS  PubMed  Google Scholar 

  23. Schmits R, Filmus J, Gerwin N et al. CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity Blood 1997 90: 2217–2233

    CAS  PubMed  Google Scholar 

  24. Rafi-Janajreh AQ, Chen D, Schmits R et al. Evidence for the involvement of CD44 in endothelial cell injury and induction of vascular leak syndrome by IL-2 J Immunol 1999 163: 1619–1627

    CAS  PubMed  Google Scholar 

  25. Boggs DR . The total marrow mass of the mouse: a simplified method of measurement Am J Hematol 1984 16: 277–286

    Article  CAS  PubMed  Google Scholar 

  26. Miller CL, Rebel VI, Lemieux ME et al. Studies of W mutant mice provide evidence for alternate mechanisms capable of activating hematopoietic stem cells Exp Hematol 1996 24: 185–194

    CAS  PubMed  Google Scholar 

  27. Lemieux ME, Rebel VI, Lansdorp PM, Eaves CJ . Characterization and purification of a primitive hematopoietic cell type in adult mouse marrow capable of lympho-myeloid differentiation in long-term marrow ‘switch’ cultures Blood 1995 86: 1339–1347

    CAS  PubMed  Google Scholar 

  28. Till JE, McCulloch EA . A direct measurement of the radiation sensitivity of normal mouse bone marrow cells Radiat Res 1961 14: 213–222

    Article  CAS  PubMed  Google Scholar 

  29. Szilvassy SJ, Humphries RK, Lansdorp PM et al. Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy Proc Natl Acad Sci USA 1990 87: 8736–8740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rebel VI, Dragowska W, Eaves CJ et al. Amplification of Sca-1+ Lin− WGA+ cells in serum-free cultures containing Steel factor, interleukin-6, and erythropoietin with maintenance of cells with long-term in vivo reconstituting potential Blood 1994 83: 128–136

    CAS  PubMed  Google Scholar 

  31. Ayroldi E, Cannarile L, Migliorati G et al. CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis Blood 1995 86: 2672–2678

    CAS  PubMed  Google Scholar 

  32. Hodgkin PD, Lee J-H, Lyons AB . B cell differentiation and isotype switching is related to division cycle number J Exp Med 1996 184: 277–281

    Article  CAS  PubMed  Google Scholar 

  33. Nordon RE, Ginsberg SS, Eaves CJ . High resolution cell division tracking demonstrates the Flt3-ligand-dependence of human marrow CD34+CD38− cell production in vitro Br J Haematol 1997 98: 528–539

    Article  CAS  PubMed  Google Scholar 

  34. Hendrikx PJ, Martens ACM, Hagenbeek A et al. Homing of fluorescently labeled murine hematopoietic stem cells Exp Hematol 1996 24: 129–140

    CAS  PubMed  Google Scholar 

  35. Lanzkron SM, Collector MI, Sharkis SJ . Hematopoietic stem cell tracking in vivo: a comparison of short-term and long-term repopulating cells Blood 1999 93: 1916–1921

    CAS  PubMed  Google Scholar 

  36. Van der Loo JCM, Ploemacher RE . Marrow- and spleen-seeding efficiencies of all murine hematopoietic stem cell subsets are decreased by preincubation with hematopoietic growth factors Blood 1995 85: 2598–2606

    CAS  PubMed  Google Scholar 

  37. Wolf NS, Kone A, Priestley GV, Bartelmez SH . In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine123 FACS selection Exp Hematol 1993 21: 614–622

    CAS  PubMed  Google Scholar 

  38. Spangrude GJ, Brooks DM, Tumas DB . Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function Blood 1995 85: 1006–1016

    CAS  PubMed  Google Scholar 

  39. Sherman L, Wainwright D, Ponta H, Herrlich P . A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb outgrowth Genes Dev 1998 12: 1058–1071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tucker AS, Al Khamis AA, Ferguson CA et al. Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development Development 1999 126: 221–228

    CAS  PubMed  Google Scholar 

  41. DeGrenedele HC, Estess P, Siegelman MH . Requirement for CD44 in activated T cell extravasation into an inflammatory site Science 1997 278: 672–675

    Article  Google Scholar 

  42. Lee T, Wisniewski HG, Vilcek J . A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44 J Cell Biol 1992 116: 545–557

    Article  CAS  PubMed  Google Scholar 

  43. Turley EA, Belch AJ, Poppema S, Pilarski LM . Expression and function of a receptor for hyaluronan-mediated motility on normal and malignant B lymphocytes Blood 1993 81: 446–453

    CAS  PubMed  Google Scholar 

  44. Banerji S, Ni J, Wang S-X et al. LYVE-1, a new homolog of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan J Cell Biol 1999 144: 789–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Pilarski LM, Pruski E, Wizniak J et al. Potential role for hyaluronan and the hyaluronan receptor RHAMM in mobilization and trafficking of hematopoietic progenitor cells Blood 1999 93: 2918–2927

    CAS  PubMed  Google Scholar 

  46. Masselis-Smith A, Belch AR, Mant MJ et al. Hyaluronan-dependent motility of B cells and leukemic plasma cells in blood but not of bone marrow plasma cells, in multiple myeloma: alternate use of receptor for hyaluronan-mediated motility (RHAMM) and CD44 Blood 1996 87: 1891–1899

    Google Scholar 

  47. Miyake K, Medina KL, Hayashi SI et al. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures J Exp Med 1990 171: 477–488

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Jessyca Maltman, Maya Sinclaire and Gayle Thornbury for excellent technical assistance, Jo-Ann Woo for typing the manuscript, Dr Tak Mak (Amgen Institute, Ontario Cancer Institute, Toronto, ON) for kindly providing the original CD44−/− breeding pairs, and Cangene and StemCell for generous gifts of reagents. This work was supported by the National Cancer Institute of Canada (NCIC) with funds from the Terry Fox Run and NIH P01 HL55435. CJ Eaves is a Terry Fox Cancer Research Scientist of the NCIC.

Author information

Authors and Affiliations

  1. The Terry Fox Laboratory, British Columbia Cancer Research Center, Canada

    RAJ Oostendorp, S Ghaffari & CJ Eaves

  2. Department of Medical Genetics, University of British Columbia, Vancouver, Canada

    CJ Eaves

Authors
  1. RAJ Oostendorp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Ghaffari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. CJ Eaves
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oostendorp, R., Ghaffari, S. & Eaves, C. Kinetics of in vivo homing and recruitment into cycle of hematopoietic cells are organ-specific but CD44-independent. Bone Marrow Transplant 26, 559–566 (2000). https://doi.org/10.1038/sj.bmt.1702536

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702536

Keywords

This article is cited by

Search

Advanced search

Quick links