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:

CD34+ Cells

Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation

Bone Marrow Transplantation volume 25, pages 377–383 (2000)Cite this article

Abstract

We characterized CD34+ cells purified from bone marrow (BM), mobilized peripheral blood (PB) and cord blood (CB) and we tried to establish correlations between the cell cycle kinetics of the CD34+CD38− and CD34+CD38+ subpopulations, their sensitivity to SCF and IL-3 and their expression of receptors for these two CSFs. At day 0, significantly fewer immature CD34+CD38− cells from CB and mobilized PB are in S + G2M phases of the cell cycle (respectively 2.0 ± 0.4 and 0.9 ± 0.3%) than their BM counterpart (5.6 ± 1.2%). A 48-h incubation with SCF + IL-3 allows a significant increase in the percentage of cycling CD34+CD38− cells in CB (19.2 ± 2.2%, P < 0.0002) and pb (14.1 ± 5.5%, P < 0.05) while the proliferative potential of bm cd34+CD38− progenitors remains constant (8.6 ± 1.0%, NS). CD123 (IL-3 receptor) expression is similar in the three sources of hematopoietic cells at day 0 and after 48-h culture. CD117 (SCF receptor) expression, although very heterogeneous according to the subpopulations and the sources of progenitors evaluated, seems not to correlate with the difference of progenitor cell sensitivity to SCF nor with their proliferative capacity. Considering the importance of the c-kit/SCF complex in the adhesion of stem cells to the microenvironment, several observations are relevant. The density of CD117 antigen expression (expressed in terms of mean equivalent soluble fluorescence, MESF) is significantly lower on fresh PB cells than on their BM (P < 0.017) and cb (P < 0.004) counterparts, particularly in the immature cd34+CD38− population (560 ± 131, 2121 ± 416 and 1192 ± 129 MESF respectively); moreover, when PB and BM CD34+CD38− cells are stimulated for 48 h with SCF + IL-3, the CD117 expression decreases by 1.5- and 1.66-fold, respectively. This reduction could modify the functional capacities of ex vivo PB and BM manipulated immature progenitor cells. Bone Marrow Transplantation (2000) 25, 377–383.

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

Similar content being viewed by others

References

  1. Arcese W, Aversa F, Bandini G et al. Clinical use of allogeneic hematopoietic stem cells from sources other than bone marrow Haematologica 1998 83: 159–182

    CAS  PubMed  Google Scholar 

  2. Rubinstein P, Carrier C, Scaradavoou A et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors New Engl J Med 1998 22: 1565–1577

    Article  Google Scholar 

  3. Traycoff CM, Abboud MR, Laver J et al. Rapid exit from G0/G1 phases of cell cycle in response to stem cell factor confers on umbilical cord blood CD34+ cells an enhanced ex vivo expansion potential Exp Hematol 1994 22: 1264–1272

    CAS  PubMed  Google Scholar 

  4. Fritsch G, Stimpfl M, Kurz M et al. The composition of CD34 subpopulations differs between bone marrow, blood and cord blood Bone Marrow Transplant 1996 17: 169–178

    CAS  PubMed  Google Scholar 

  5. Wang JCY, Doedens M, Dick JE . Primitive human hematopoietic cells are enriched in cord blood compared with adult bone marrow or mobilized peripheral blood as measured by the quantitative in vivo SCID-repopulating cell assay Blood 1997 89: 3919–3924

    CAS  Google Scholar 

  6. Almici C, Carlo-Stella C, Wagner JE et al. Biologic and phenotypic analysis of early hematopoietic progenitor cells in umbilical cord blood Leukemia 1997 11: 2143–2149

    Article  CAS  Google Scholar 

  7. Reems JA, Torok-Sorb B . Cell cycle and functional differences between CD34+/CD38hi and CD34+/CD38lo human marrow cells after in vitro cytokine exposure Blood 1995 85: 1480–1487

    CAS  PubMed  Google Scholar 

  8. Terstappen LWMM, Huang S, Safford M et al. Sequential generations of hematopoietic colonies derived from single nonlineage committed progenitor cells Blood 1991 77: 1218–1227

    CAS  PubMed  Google Scholar 

  9. Civin CI, Almeida-porada G, Lee MJ et al. Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo Blood 1996 88: 4102–4109

    CAS  PubMed  Google Scholar 

  10. Hao Q-L, Shah AJ, Thiemann FT et al . A functional comparison of CD34+CD38− cells in cord blood and bone marrow Blood 1995 86: 3745–3753

    CAS  Google Scholar 

  11. De Bruyn C, Delforge A, Bron D et al. Ex vivo expansion of CD34+CD38− cord blood cells J Hematother 1997 6: 93–102

    Article  CAS  Google Scholar 

  12. Gordon MY, Dowding CR, Riley GP, Greaves MF . Characterisation of stroma-dependent blast colony forming cells in human marrow J Cell Physiol 1987 130: 150–156

    Article  CAS  Google Scholar 

  13. Gordon MY, Lewis JL, Grand FH et al. Phenotype and progeny of primitive adherent human hematopoietic progenitors Leukemia 1996 10: 1347–1353

    CAS  PubMed  Google Scholar 

  14. De Bruyn C, Delforge A, Bron D et al. Comparison of the coexpression of CD38, CD33 and HLA-DR antigens on CD34+ purified cells from human cord blood and bone marrow Stem Cells 1995 13: 281–288

    Article  CAS  Google Scholar 

  15. Srour EF, Bregni M, Traycoff CM et al. Long term hematopoietic culture-initiating cells are more abundant in mobilized peripheral blood graft than in bone marrow but have a more limited ex vivo expansion potential Blood Cells Mol Dis 1996 22: 68–81

    Article  CAS  Google Scholar 

  16. Weekx SFA, Van Bockstaele DR, Plum J et al. CD34++CD38− and CD34+CD38+ human hematopoietic progenitors from fetal liver, cord blood and adult bone marrow respond differently to hematopoietic cytokines depending on the ontogenic source Exp Hematol 1998 26: 1034–1042

    CAS  Google Scholar 

  17. Mielcarek M, Torok-Storb B . Phenotype and engraftment potential of cytokine-mobilized peripheral blood mononuclear cells Curr Opin Hematol 1997 4: 176–182

    Article  CAS  Google Scholar 

  18. Donahue RE, Kirby MR, Metzger ME et al. Peripheral blood CD34+ cells differ from bone marrow CD34+ cells in thy-1 expression and cell cycle status in nonhuman primates mobilized or not mobilized with granulocyte colony-stimulating factor and/or stem cell factor Blood 1996 87: 1644–1653

    CAS  PubMed  Google Scholar 

  19. Leitner A . Lack of DNA synthesis among CD34+ cells in cord blood and in cytokine-mobilized blood Br J Haematol 1996 92: 255–262

    Article  CAS  Google Scholar 

  20. Uchida N, He D, Friera AM et al. The unexpected G0/G1 cell cycle status of mobilized hematopoietic stem cells from peripheral blood Blood 1997 89: 465–472

    CAS  PubMed  Google Scholar 

  21. Yamaguchi M, Ikebuchi K, Hirayama F et al. Different adhesive characteristics and VLA-4 expression of CD34+ progenitors in G0/G1 versus S+G2/M phases of the cell cycle Blood 1998 92: 842–848

    CAS  PubMed  Google Scholar 

  22. Croockewit AJ, Raymakers RA, Smeets ME et al. The low cycling status of mobilized peripheral blood CD34+ cells is not restricted to the more primitive subfraction Leukemia 1998 12: 571–577

    Article  CAS  Google Scholar 

  23. Lemoli RM, Tafuri A et al. Cycling status of CD34+ cells mobilized into peripheral blood of healthy donors by recombinant human granulocyte colony-stimulating factor Blood 1997 89: 1189–1196

    CAS  PubMed  Google Scholar 

  24. Ratajczak MZ, Pletcher CH, Marlicz W et al. CD34+, kit+, rhodamine 123 low phenotype identifies a marrow cell population highly enriched for human hematopoietic stem cells Leukemia 1998 12: 942–950

    Article  CAS  Google Scholar 

  25. Doi H, Inaba M, Yamamoto Y et al. Pluripotent hematopoietic stem cells are c-kit &lt;low Proc Natl Acad Sci USA 1997 94: 2513–2517

    Article  CAS  Google Scholar 

  26. Sogo S, Inaba M, Ogata H et al. Induction of c-kit molecules on human CD34+/c-kit &lt;low cells: evidence for CD34+/c-kit &lt;low cells as primitive hematopoietic stem cells Stem Cells 1997 15: 420–429

    Article  CAS  Google Scholar 

  27. Sakabe H, Ohmizono Y, Tanimukai S et al. Functional differences between subpopulations of mobilized peripheral blood-derived CD34+ cells expressing different levels of HLA-DR, CD33, CD38 and c-kit antigens Stem Cells 1997 15: 73–81

    Article  CAS  Google Scholar 

  28. Sakabe H, Yahata N, Kimura T et al. Human cord blood-derived primitive progenitors are enriched in CD34+c-kit− cells: correlation between long-term culture-initiating cells and telomerase expression Leukemia 1998 12: 728–734

    Article  CAS  Google Scholar 

  29. Steen R, Tjonnfjord GE, Groseth GLA et al. Efflux of CD34+ cells from bone marrow to peripheral blood is selective in steady-state hematopoiesis and during G-CSF administration J Hematother 1997 6: 563–573

    Article  CAS  Google Scholar 

  30. Kroger N, Zeller W, Hassan HT et al. Difference between expression of adhesion molecules on CD34+ cells from bone marrow and G-CSF-stimulated peripheral blood Stem Cells 1998 16: 49–53

    Article  CAS  Google Scholar 

  31. Broudy VC . Stem cell factor and hematopoiesis Blood 1997 90: 1345–1364

    CAS  PubMed  Google Scholar 

  32. D'Arena G . Thy-1 (CDw90) and c-kit receptor (CD117) expression on CD34+ hematopoietic progenitor cells: a five dimensional flow cytometry study Haematologica 1998 83: 587–592

    CAS  PubMed  Google Scholar 

  33. Kodama H, Nose M, Niida S et al. Involvement of the c-kit receptor in the adhesion of hematopoietic stem cells to stromal cells Exp Hematol 1994 22: 979–984

    CAS  PubMed  Google Scholar 

  34. Gothot A, van der Loo JCM, Clapp DW, Srour EF . Cell cycle related changes in repopulating capacity of human mobilized peripheral blood CD34+ cells in non-obese diabetic/severe combined immune-deficient mice Blood 1998 92: 2641–2649

    CAS  PubMed  Google Scholar 

  35. 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 

  36. Alcorn MJ, Holyoake TL, Richmond L et al. CD34 positive cells isolated from cryopreserved peripheral blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity J Clin Oncol 1996 14: 1839–1847

    Article  CAS  Google Scholar 

  37. Holyoake TL, Alcorn MJ, Richmond L et al. CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens Bone Marrow Transplant 1997 19: 1095–1101

    Article  CAS  Google Scholar 

  38. Stiff P, Oldenberg D, Hsi E et al. Transplantation of ex vivo expanded cells grown in an Aastrom stromal-based perfusion bioreactor from small marrow aliquots (40ml) produces durable hematopoietic reconstitution after ablative chemotherapy Blood 1997 90: (Suppl.1) 395a

    Google Scholar 

Download references

Acknowledgements

We thank Amgen for providing us with SCF. C De Bruyn is supported by grant FNRS-Télévie No. 7.4503.98.

Author information

Authors and Affiliations

  1. Service de Médecine Interne et Laboratoire de Recherche et d'Investigation Clinique, Institut J Bordet, Brussels, Belgium

    C De Bruyn, A Delforge, L Lagneaux & D Bron

Authors
  1. C De Bruyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Delforge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Lagneaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D Bron
    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

De Bruyn, C., Delforge, A., Lagneaux, L. et al. Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation. Bone Marrow Transplant 25, 377–383 (2000). https://doi.org/10.1038/sj.bmt.1702145

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702145

Keywords

This article is cited by

Search

Advanced search

Quick links