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CD34+ Cells

Absence of a CD34− hematopoietic precursor population in recipients of CD34+ stem cell transplantation

Bone Marrow Transplantation volume 28, pages 587–595 (2001)Cite this article

Abstract

The purified CD34+ cell fraction has been used for hematopoietic stem cell transplantation since they were demonstrated to have long-term reconstituting ability. Therefore, the potential effects of CD34− stem cells on the clinical course have been a major concern in recipients of CD34+-selected transplantation. To address this concern, we used an in vitro assay to determine whether transplant recipients have CD34−precursor population. Lin−CD34− cells were isolated from bone marrow cells in 11 transplant recipients including four CD34-selected transplantations, six standard bone marrow transplantations, and one T cell-depleted marrow transplantation. The frequency of the Lin−CD34− population in four CD34-enriched transplantation recipients was not different from those of normal donors or recipients of other modes of transplantation: 0.96 ± 1.01% (mean ± s.d., n = 4), 0.45 ± 0.16% (n = 6), and 0.66 ± 0.59% (n = 7), respectively. However, the Lin−CD34−population obtained from the recipients of CD34-enriched transplantation acquired neither CD34 expression nor colony-forming activity after 7 days of culture, whereas the cells from all the normal individuals and standard BMT recipients were able to differentiate into CD34+ cells accompanied by the emergence of colony-forming activity. We conclude that recipients of CD34-enriched transplantation appear to have defects in their CD34− precursor population. The clinical significance of these defects will be determined in a life-long follow-up of these patients. Bone Marrow Transplantation (2001) 28, 587–595.

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References

  1. Berenson RJ, Andrews RG, Bensinger WI et al. Antigen CD34+ marrow cells engraft lethally irradiated baboons J Clin Invest 1988 81: 951–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bodine DM, Moritz T, Donahue RE et al. Long-term in vivo expression of a murine adenosine deaminase gene in rhesus monkey hematopoietic cells of multiple lineages after retroviral mediated gene transfer into CD34+ bone marrow cells Blood 1993 82: 1975–1980

    CAS  PubMed  Google Scholar 

  3. Krause DS, Mucenski ML, Lawler AM, May WS . CD34 expression by embryonic hematopoietic and endothelial cells does not require c-Myb Exp Hematol 1998 26: 1086–1092

    CAS  PubMed  Google Scholar 

  4. Berenson RJ, Bensinger WI, Hill RS et al. Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma Blood 1991 77: 1717–1722

    CAS  PubMed  Google Scholar 

  5. Corringham RE, Ho AD . Rapid and sustained allogeneic transplantation using immunoselected CD34(+)-selected peripheral blood progenitor cells mobilized by recombinant granulocyte and granulocyte–macrophage colony-stimulating factors (letter) Blood 1995 86: 2052–2054

    CAS  PubMed  Google Scholar 

  6. Yabe H, Yabe M, Hattori K et al. Successful engraftment of allogeneic CD34-enriched marrow cell transplantation from HLA-mismatched parental donors Bone Marrow Transplant 1996 17: 985–991

    CAS  PubMed  Google Scholar 

  7. Link H, Arseniev L, Bahre O et al. Transplantation of allogeneic CD34+ blood cells Blood 1996 87: 4903–4909

    CAS  PubMed  Google Scholar 

  8. Kawano Y, Takaue Y, Watanabe A et al. Partially mismatched pediatric transplants with allogeneic CD34(+) blood cells from a related donor Blood 1998 92: 3123–3130

    CAS  PubMed  Google Scholar 

  9. Kato S, Yabe H, Yasui M et al. Allogeneic hematopoietic transplantation of CD34+ selected cells from an HLA haplo-identical related donor. A long-term follow-up of 135 patients and a comparison of stem cell source between the bone marrow and the peripheral blood Bone Marrow Transplant 2000 26: 1281–1290

    Article  CAS  PubMed  Google Scholar 

  10. Osawa M, Hanada K, Hamada H, Nakauchi H . Long-term lymphohematopoietic reconstitution by a single CD34− low/negative hematopoietic stem cell Science 1996 273: 242–245

    Article  CAS  PubMed  Google Scholar 

  11. Goodell MA, Rosenzweig M, Kim H et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species Nature Med 1997 3: 1337–1345

    Article  CAS  PubMed  Google Scholar 

  12. Morel F, Galy A, Chen B, Szilvassy SJ . Equal distribution of competitive long-term repopulating stem cells in the CD34+ and CD34− fractions of Thy-1lowLin−/lowSca-1+ bone marrow cells Exp Hematol 1998 26: 440–448

    CAS  PubMed  Google Scholar 

  13. Sato T, Laver JH, Ogawa M . Reversible expression of CD34 by murine hematopoietic stem cells Blood 1999 94: 2548–2554

    CAS  PubMed  Google Scholar 

  14. Zanjani ED, Almeida-Porada G, Livingston AG et al. Human bone marrow CD34− cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells Exp Hematol 1998 26: 353–360

    CAS  PubMed  Google Scholar 

  15. Bhatia M, Bonnet D, Murdoch B et al. A newly discovered class of human hematopoietic cells with SCID-repopulating activity Nature Med 1998 4: 1038–1045

    Article  CAS  PubMed  Google Scholar 

  16. Nakauch H . Hematopoietic stem cells Are they CD34-positive or CD34-negative? Nature Med 1998 4: 1009–1010

    Article  Google Scholar 

  17. Nakamura Y, Ando K, Chargui J et al. Ex vivo generation of CD34 positive cells from CD34 negative hematopoietic cells Blood 1999 94: 4053–4059

    CAS  PubMed  Google Scholar 

  18. Ando K, Nakamura Y, Chargui J et al. Extensive generation of human cord blood CD34(+) stem cells from Lin(−)CD34(−) cells in a long-term in vitro system Exp Hematol 2000 28: 690–699

    Article  CAS  PubMed  Google Scholar 

  19. Tsuji T, Ogasawara H, Aoki Y et al. Characterization of murine stromal cell clones established from bone marrow and spleen Leukemia 1996 10: 803–812

    CAS  PubMed  Google Scholar 

  20. Kawada H, Ando K, Tsuji T et al. Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system Exp Hematol 1999 27: 904–915

    Article  CAS  PubMed  Google Scholar 

  21. Katsuyama Y, Inoko H, Imanishi T et al. Genetic relationships among Japanese, northern Han, Hui, Uygur, Kazakh, Greek, Saudi Arabian, and Italian populations based on allelic frequencies at four VNTR (D1S80, D4S43, COL2A1, D17S5) and one STR (ACTBP2) loci Hum Hered 1998 48: 126–137

    Article  CAS  PubMed  Google Scholar 

  22. Zanjani ED, Almeida-Porada G, Livingston AG et al. Long-term engrafting capabilities of CD34-negative human adult marrow cells Blood 1998 92: 504a

    Google Scholar 

  23. Fujisaki T, Berger MG, Rose-John S, Eaves CJ . Rapiddifferentiation of a rare subset of adult human lin(−)CD34(−)CD38(−) cells stimulated by multiple growth factors in vitro Blood 1999 94: 1926–1932

    CAS  PubMed  Google Scholar 

  24. Kim DK, Fujiki Y, Fukushima T et al. Comparison of hematopoietic activities of human bone marrow and umbilical cord blood CD34 positive and negative cells Stem Cells 1999 17: 286–294

    Article  CAS  PubMed  Google Scholar 

  25. Bhatia M, Wang J, Kapp U et al. 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 

  26. Ziegler BL, Valtieri M, Porada GA et al. KDR receptor: a key marker defining hematopoietic stem cells Science 1999 285: 1553–1558

    Article  CAS  PubMed  Google Scholar 

  27. Nakamura Y, Ando K . Sumita M et al. Effective enrichment of the precursor populations of human CD34+ hematopoietic cells by newly developed filter system Br J Haematol 2000 108: 801–804

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Hideyuki Matsuzawa for his excellent technical assistance, Shizuko Imai for secretarial work and the members of Tokai CBSC Study Group for their assistance. The authors also wish to thank KIRIN Brewery Co. Ltd. for supplying various growth factors. This study was supported by The Japan Society for the Promotion of Science (JSPS) grant no. JSPS-RFTF97 I 00201 and a research grant of the science Frontier Program from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Research Center for Cell Transplantation, Tokai University, School of Medicine, Kanagawa, Japan

    S Kato, K Ando, Y Nakamura, Y Muguruma, T Sato & T Hotta

  2. Department of Pediatrics, Research Center for Cell Transplantation, Tokai University, School of Medicine, Kanagawa, Japan

    S Kato, H Yabe, M Yabe, K Hattori & Y Yasuda

  3. Department of Hematology, Research Center for Cell Transplantation, Tokai University, School of Medicine, Kanagawa, Japan

    K Ando & T Hotta

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  1. S Kato
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Kato, S., Ando, K., Nakamura, Y. et al. Absence of a CD34− hematopoietic precursor population in recipients of CD34+ stem cell transplantation. Bone Marrow Transplant 28, 587–595 (2001). https://doi.org/10.1038/sj.bmt.1703186

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