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Progenitor Cell Homing

Enumeration of bone marrow ‘homing’ haemopoietic stem cells from G-CSF-mobilised normal donors and influence on engraftment following allogeneic transplantation

Abstract

Expression of the chemokine receptor CXCR4 on human haemopoietic stem cells (HSC) may play a crucial role in localising these cells to the bone marrow. To evaluate whether CXCR4 expression is clinically relevant we have enumerated CXCR4-positive HSC used for allogeneic transplantation and sought any relationship with the rate of subsequent haemopoietic reconstitution. CD34-positive progenitor cells were isolated from peripheral blood stem cell (PBSC) collections from 16 normal donors. The proportion of cells co-expressing CXCR4 was enumerated and the times to recipient haemopoietic reconstitution measured. The median frequency of CD34-positive cells co-expressing CXCR4 was 41% (range 16% to 76%) and the median number of CXCR4 CD34 double-positive cells infused at transplantation was 2.5 × 106 cells/kg (range 0.8–10.3). Patients receiving >2.5 × 106 CXCR4 CD34 double-positive cells/kg demonstrated a significant shortening of time to platelet engraftment compared to the recipients of the lower cell doses (10 days vs 14.5 days, respectively, P = 0.02) with all but one of the recipients of the higher cell doses achieving platelet engraftment by day 11. Co-expression of CXCR4 on CD34-positive progenitor cells may be an important determinant of post-transplant engraftment and in our hands transplantation of a minimum of 2.5 × 106 CXCR4 CD34 double-positive cells/kg ensured rapid post-transplant platelet recovery.

Bone Marrow Transplantation (2001) 28, 1019–1022.

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References

  1. Mohle R, Bautz F, Rafii S et al. 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 1998 91: 4523–4530

    CAS  PubMed  Google Scholar 

  2. Deog-Yeon J, Rafii S, Hamada T, Moore MAS . Chemotaxis of primitive hematopoietic cells in response to stromal cell-derived factor-1 J Clin Invest 2000 105: 101–111

    Article  Google Scholar 

  3. Peled A, Petit I, Kollet O et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4 Science 1999 283: 845–848

    Article  CAS  PubMed  Google Scholar 

  4. Sutherland DR, Anderson L, Keeney M et al. The ISHAGE guidelines for CD34+ cell determination by flow cytometry J Hematother 1996 5: 213–216

    Article  CAS  PubMed  Google Scholar 

  5. Yong K, Fahey A, Reeve L et al. Cord blood progenitor cells have greater transendothelial migratory activity and increased responses to SDF-1 and MIP-3beta compared with mobilized adult progenitor cells Br J Haematol 1999 107: 441–449

    Article  CAS  PubMed  Google Scholar 

  6. To LB, Haylock DN, Simmons PJ, Juttner CA . The biology and clinical uses of blood stem cells (review) Blood 1997 89: 2233–2258

    CAS  PubMed  Google Scholar 

  7. Weaver CH, Hazelton B, Birch R et al. 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 1995 86: 3961–3969

    CAS  PubMed  Google Scholar 

  8. Tricot G, Jagannath S, Vesole D et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favourable variables for rapid engraftment in 225 patients Blood 1995 85: 588–597

    CAS  PubMed  Google Scholar 

  9. Ketterer N, Salles G, Raba M et al. High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral blood progenitor cell transplantation Blood 1998 91: 3148–3155

    CAS  PubMed  Google Scholar 

  10. Bhatia M, Wang J, Kapp U . Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice Proc Natl Acad Sci USA 1997 94: 5320–5325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rosu-Myles M, Gallacher B, Murdoch B et al. The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression Proc Natl Acad Sci USA 2000 97: 14626–14631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Aiuti A, Web IJ, Bleul C et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood J Exp Med 1997 185: 111–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was funded in part by the Anderson Trust and by Amgen Australia.

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Spencer, A., Jackson, J. & Baulch-Brown, C. Enumeration of bone marrow ‘homing’ haemopoietic stem cells from G-CSF-mobilised normal donors and influence on engraftment following allogeneic transplantation. Bone Marrow Transplant 28, 1019–1022 (2001). https://doi.org/10.1038/sj.bmt.1703289

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