Skip to main content

Thank you for visiting 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.

Stem cell transplantation

Characteristics of cells with engraftment capacity within CD34+ cell population upon G-CSF and Plerixafor mobilization


In the context of hematopoietic cell transplantation, hematopoietic stem cells and progenitor cells (HSC and HPC) are usually collected by apheresis following their mobilization by G-CSF alone or in combination with Plerixafor® when patients fail to respond to G-CSF alone. In medical practice, the quality of the hematopoietic graft is based on CD34+ cell content that is used to define “Good Mobilizer (GM)” or “Poor Mobilizer (PM)” patients but does not report the real HSC content of grafts. In this study, we assessed the HSC content within the CD34+ fraction of graft samples from 3 groups of patients: 1-GM patients receiving G-CSF only (GMG-CSF), 2-PM patients receiving G-CSF only (PMG-CSF), 3-PM patients receiving G-CSF + Plerixafor (PMG-CSF+P). Although HSC from the 3 groups of patients displayed very similar phenotypic profiles, expression of “stemness” genes and metabolic characteristics, their capacity to engraft NSG mice differed revealing differences in terms of HSC between groups. Indeed according to mobilization regimen, we observed differences in migration capacity of HSC, as well as differences in engraftment intensity depending on the initial pathology (myeloma versus lymphoma) of patients. This suggests that mobilization regimen could strongly influence the long term engraftment efficiency of hematopoietic grafts.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Characterization of SP cells from healthy donors, GM and PM patients according to mobilization regimen.
Fig. 2: Relative quantification of stemness genes.
Fig. 3: Mitochondrial characteristics, glucose uptake, and ROS content.
Fig. 4: Committed and immature progenitor potential of SP/CD34+ cells.
Fig. 5: SCID-repopulating cell potential of SP/CD34+ cells.


  1. 1.

    Hopman RK, DiPersio JF. Advances in stem cell mobilization. Blood Rev. 2014;28(1):31–40.

    CAS  Article  Google Scholar 

  2. 2.

    Transfusion. ECoB. Guide to the preparation, use and quality assurance of blood components. In: HealthCare EDftQoM, editor. 19th ed; 2017.

  3. 3.

    In: Carreras E, Dufour C, Mohty M, Kroger N (eds). The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies: Cham (CH), 2019.

  4. 4.

    Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR. et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109:625–37.

    CAS  Article  Google Scholar 

  5. 5.

    Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. 2002;3:687–94.

    CAS  Article  Google Scholar 

  6. 6.

    Domingues MJ, Nilsson SK, Cao B. New agents in HSC mobilization. Int J Hematol. 2017;105:141–52.

    CAS  Article  Google Scholar 

  7. 7.

    Girbl T, Lunzer V, Greil R, Namberger K, Hartmann TN. The CXCR4 and adhesion molecule expression of CD34+ hematopoietic cells mobilized by “on-demand” addition of plerixafor to granulocyte-colony-stimulating factor. Transfusion. 2014;54:2325–35.

    CAS  Article  Google Scholar 

  8. 8.

    To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. Blood. 2011;118(17):4530–40.

    CAS  Article  Google Scholar 

  9. 9.

    Fricker SP, Anastassov V, Cox J, Darkes MC, Grujic O, Idzan SR, et al. Characterization of the molecular pharmacology of AMD3100: a specific antagonist of the G-protein coupled chemokine receptor, CXCR4. Biochem Pharm. 2006;72:588–96.

    CAS  Article  Google Scholar 

  10. 10.

    Martin C, Bridger GJ, Rankin SM. Structural analogues of AMD3100 mobilise haematopoietic progenitor cells from bone marrow in vivo according to their ability to inhibit CXCL12 binding to CXCR4 in vitro. Br J Haematol. 2006;134:326–9.

    CAS  Article  Google Scholar 

  11. 11.

    Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD, et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005;106:1867–74.

    CAS  Article  Google Scholar 

  12. 12.

    Calandra G, McCarty J, McGuirk J, Tricot G, Crocker SA, Badel K. et al. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin’s lymphoma, Hodgkin’s disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data. Bone marrow Transplant. 2008;41:331–8.

    CAS  Article  Google Scholar 

  13. 13.

    Esrick EB, Manis JP, Daley H, Baricordi C, Trebeden-Negre H, Pierciey FJ, et al. Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients. Blood Adv. 2018;2(19):2505–12.

    CAS  Article  Google Scholar 

  14. 14.

    Devine SM, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N, et al. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood. 2008;112:990–8.

    CAS  Article  Google Scholar 

  15. 15.

    Schroeder MA, Rettig MP, Lopez S, Christ S, Fiala M, Eades W, et al. Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft. Blood. 2017;129(19):2680–92.

    CAS  Article  Google Scholar 

  16. 16.

    Couban S, Wong PC, Schultz KR. The case for plerixafor to replace filgrastim as the optimal agent to mobilize peripheral blood donors for allogeneic hematopoietic cell transplantation. Exp Hematol. 2019;70:1–9.

    CAS  Article  Google Scholar 

  17. 17.

    Fruehauf S, Veldwijk MR, Seeger T, Schubert M, Laufs S, Topaly J. et al. A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study. Cytotherapy. 2009;11:992–1001.

    CAS  Article  Google Scholar 

  18. 18.

    Lidonnici MR, Aprile A, Frittoli MC, Mandelli G, Paleari Y, Spinelli A, et al. Plerixafor and G-CSF combination mobilizes hematopoietic stem and progenitors cells with a distinct transcriptional profile and a reduced in vivo homing capacity compared to plerixafor alone. Haematologica. 2017;102:e120–e124.

    Article  Google Scholar 

  19. 19.

    Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797–806.

    CAS  Article  Google Scholar 

  20. 20.

    Goodell MA. Multipotential stem cells and ‘side population’ cells. Cytotherapy. 2002;4:507–8.

    CAS  Article  Google Scholar 

  21. 21.

    Pierre-Louis O, Clay D, Brunet de la Grange P, Blazsek I, Desterke C, Guerton B, et al. Dual SP/ALDH functionalities refine the human hematopoietic Lin-CD34+CD38- stem/progenitor cell compartment. Stem cells. 2009;27(10):2552–62.

    CAS  Article  Google Scholar 

  22. 22.

    Bourdieu A, Avalon M, Lapostolle V, Ismail S, Mombled M, Debeissat C, et al. Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells. J Cell Physiol. 2018;233:338–49.

    CAS  Article  Google Scholar 

  23. 23.

    Brunet de la Grange P, Vlaski M, Duchez P, Chevaleyre J, Lapostolle V, Boiron JM, et al. Long-term repopulating hematopoietic stem cells and “side population” in human steady state peripheral blood. Stem cell Res. 2013;11:625–33.

    CAS  Article  Google Scholar 

  24. 24.

    Ivanovic Z, Belloc F, Faucher JL, Cipolleschi MG, Praloran V, Dello Sbarba P. Hypoxia maintains and interleukin-3 reduces the pre-colony-forming cell potential of dividing CD34(+) murine bone marrow cells. Exp Hematol. 2002;30:67–73.

    CAS  Article  Google Scholar 

  25. 25.

    Desplat V, Faucher JL, Mahon FX, Dello Sbarba P, Praloran V, Ivanovic Z. Hypoxia modifies proliferation and differentiation of CD34(+) CML cells. Stem cells. 2002;20:347–54.

    CAS  Article  Google Scholar 

  26. 26.

    DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113(23):5720–6.

    CAS  Article  Google Scholar 

  27. 27.

    Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med. 2005;201:1307–18.

    CAS  Article  Google Scholar 

  28. 28.

    Hess DA, Bonde J, Craft TP, Wirthlin L, Hohm S, Lahey R, et al. Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor. Biol Blood Marrow Transplant. 2007;13:398–411.

    CAS  Article  Google Scholar 

Download references


We are grateful to Vincent Pitard, Anaelle Stum, Valérie De Luca, and Atika Zouine from UB’Facsility Plateform (TBMCore Platforms UMS 3427/US 005) for cell sorting; Xavier Gauthereau from PCRq’UB Platform (TBMCore Platforms UMS 3427/US 005) for qPCR analysis; Benoît Rousseau, Julien Izotte and all the staff of the A2 Animal Housing from “Service Commun des Animaleries”, University of Bordeaux. We are also grateful to the staff of “Centre de santé” of Nouvelle Aquitaine-French Blood Institute. This work was supported by a grant from French Blood Institute (APR 2014).

Author information




M.M. performed research and analyzed the data. L.R., M.A., and P.D. performed the research. C.D. performed the research and read the paper, B.P. performed research, M.V.L. and J.M.P. performed critical reading, C.M.S. corrected and improved the paper, F.T. and T.C. provided cell samples, F.T. designed the experiment and performed critical reading, Z.I. analyzed the data and performed critical reading. P.B.G designed the research, analyzed the data, and. wrote the paper.

Corresponding author

Correspondence to Philippe Brunet de la Grange.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mombled, M., Rodriguez, L., Avalon, M. et al. Characteristics of cells with engraftment capacity within CD34+ cell population upon G-CSF and Plerixafor mobilization. Leukemia 34, 3370–3381 (2020).

Download citation

Further reading


Quick links