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Stem Cell Procurement

Graft source determines human hematopoietic progenitor distribution pattern within the CD34+ compartment

Bone Marrow Transplantation volume 46, pages 650–658 (2011)Cite this article

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Abstract

The CD34+ compartment of grafts for clinical allogeneic hematopoietic cell transplantation (HCT) is very heterogeneous. It contains hematopoietic stem cells and several different progenitor cell populations. This study assesses (1) the content of these populations in clinical grafts from G-CSF-mobilized PBMCs, BM and cord blood, (2) the functional correlation of the graft composition with time to engraftment of neutrophils, platelets and reticulocytes and (3) donor age-related changes. Quantitative flow cytometry showed that the distribution of the progenitor subsets differed significantly between the graft sources and that donor age-related changes occur. In patients after myeloablative allogeneic HCT, accelerated platelet and reticulocyte engraftment correlated with the content of common myeloid and/or megakaryocyte erythroid progenitors in the graft. These findings show that a better understanding of the progenitor compartment in human hematopoietic grafts could lead to improved strategies for the development of cellular therapies, for example in situations where platelet engraftment is delayed.

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References

  1. Heimfeld S . HLA-identical stem cell transplantation: is there an optimal CD34 cell dose? Bone Marrow Transplant 2003; 31: 839–845.

    Article  CAS  PubMed  Google Scholar 

  2. Pulsipher MA, Chitphakdithai P, Logan BR, Leitman SF, Anderlini P, Klein JP et al. Donor, recipient, and transplant characteristics as risk factors after unrelated donor PBSC transplantation: beneficial effects of higher CD34+ cell dose. Blood 2009; 114: 2606–2616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zaucha JM, Gooley T, Bensinger WI, Heimfeld S, Chauncey TR, Zaucha R et al. CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation. Blood 2001; 98: 3221–3227.

    Article  CAS  PubMed  Google Scholar 

  4. Cao TM, Wong RM, Sheehan K, Laport GG, Stockerl-Goldstein KE, Johnston LJ et al. CD34, CD4, and CD8 cell doses do not influence engraftment, graft-versus-host disease, or survival following myeloablative human leukocyte antigen-identical peripheral blood allografting for hematologic malignancies. Exp Hematol 2005; 33: 279–285.

    Article  PubMed  Google Scholar 

  5. Nakamura R, Auayporn N, Smith DD, Palmer J, Sun JY, Schriber J et al. Impact of graft cell dose on transplant outcomes following unrelated donor allogeneic peripheral blood stem cell transplantation: higher CD34+ cell doses are associated with decreased relapse rates. Biol Blood Marrow Transplant 2008; 14: 449–457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–181.

    CAS  PubMed  Google Scholar 

  7. Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF et al. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol 2003; 21: 759–806.

    Article  CAS  PubMed  Google Scholar 

  8. Weissman IL, Shizuru JA . The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood 2008; 112: 3543–3553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Blom B, Spits H . Development of human lymphoid cells. Annu Rev Immunol 2006; 24: 287–320.

    Article  CAS  PubMed  Google Scholar 

  10. Baum CM, Weissman IL, Tsukamoto AS, Buckle AM, Peault B . Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci USA 1992; 89: 2804–2808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Manz MG, Miyamoto T, Akashi K, Weissman IL . Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci USA 2002; 99: 11872–11877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hao QL, Zhu J, Price MA, Payne KJ, Barsky LW, Crooks GM . Identification of a novel, human multilymphoid progenitor in cord blood. Blood 2001; 97: 3683–3690.

    Article  CAS  PubMed  Google Scholar 

  13. Galy A, Travis M, Cen D, Chen B . Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity 1995; 3: 459–473.

    Article  CAS  PubMed  Google Scholar 

  14. Kikushige Y, Yoshimoto G, Miyamoto T, Iino T, Mori Y, Iwasaki H et al. Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. J Immunol 2008; 180: 7358–7367.

    Article  CAS  PubMed  Google Scholar 

  15. Na Nakorn T, Traver D, Weissman IL, Akashi K . Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S. J Clin Invest 2002; 109: 1579–1585.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Arber C, Bitmansour A, Shashidhar S, Wang S, Tseng B, Brown JM . Protection against lethal Aspergillus fumigatus infection in mice by allogeneic myeloid progenitors is not major histocompatibility complex restricted. J Infect Dis 2005; 192: 1666–1671.

    Article  CAS  PubMed  Google Scholar 

  17. Arber C, BitMansour A, Sparer TE, Higgins JP, Mocarski ES, Weissman IL et al. Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation. Blood 2003; 102: 421–428.

    Article  CAS  PubMed  Google Scholar 

  18. Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci USA 2005; 102: 9194–9199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman IL, Bryder D et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci USA 2010; 107: 5465–5470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I . The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J Hematother 1996; 5: 213–226.

    Article  CAS  PubMed  Google Scholar 

  21. d'Onofrio G, Tichelli A, Foures C, Theodorsen L . Indicators of haematopoietic recovery after bone marrow transplantation: the role of reticulocyte measurements. Clin Lab Haematol 1996; 18 (Suppl 1): 45–53.

    PubMed  Google Scholar 

  22. Imamura R, Miyamoto T, Yoshimoto G, Kamezaki K, Ishikawa F, Henzan H et al. Mobilization of human lymphoid progenitors after treatment with granulocyte colony-stimulating factor. J Immunol 2005; 175: 2647–2654.

    Article  CAS  PubMed  Google Scholar 

  23. Favre G, Beksac M, Bacigalupo A, Ruutu T, Nagler A, Gluckman E et al. Differences between graft product and donor side effects following bone marrow or stem cell donation. Bone Marrow Transplant 2003; 32: 873–880.

    Article  CAS  PubMed  Google Scholar 

  24. Kollman C, Howe CW, Anasetti C, Antin JH, Davies SM, Filipovich AH et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2001; 98: 2043–2051.

    Article  CAS  PubMed  Google Scholar 

  25. Bautista G, Cabrera JR, Regidor C, Fores R, Garcia-Marco JA, Ojeda E et al. Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor. Bone Marrow Transplant 2009; 43: 365–373.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the Stem Cell Transplantation Team and the Flow Cytometry Laboratory of the Department of Laboratory Medicine at the University Hospital Basel. Financial support for CA was provided by Krebsliga beider Basel.

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Author notes

  1. C Arber

    Present address: 2Current address: Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, 1102 Bates Street, Suite 1770, Houston, TX 77030, USA.,

Authors and Affiliations

  1. Department of Medicine, Hematology, University Hospital Basel, Basel, Switzerland

    C Arber, J Halter, M Stern, A Rovó, A Gratwohl & A Tichelli

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  1. C Arber
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Correspondence to C Arber.

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Arber, C., Halter, J., Stern, M. et al. Graft source determines human hematopoietic progenitor distribution pattern within the CD34+ compartment. Bone Marrow Transplant 46, 650–658 (2011). https://doi.org/10.1038/bmt.2010.193

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  • DOI: https://doi.org/10.1038/bmt.2010.193

Keywords

  • human hematopoietic stem cells
  • common myeloid progenitors
  • graft composition
  • engraftment
  • allogeneic hematopoietic cell transplantation
  • donor age

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