Stem cell transplantation

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

Abstract

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.

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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.

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Acknowledgements

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).

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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.

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Correspondence to Philippe Brunet de la Grange.

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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 (2020). https://doi.org/10.1038/s41375-020-0982-y

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