Human erythroid cells produced ex vivo at large scale differentiate into red blood cells in vivo

Abstract

New sources of red blood cells (RBCs) would improve the transfusion capacity of blood centers. Our objective was to generate cells for transfusion by inducing a massive proliferation of hematopoietic stem and progenitor cells, followed by terminal erythroid differentiation. We describe here a procedure for amplifying hematopoietic stem cells (HSCs) from human cord blood (CB) by the sequential application of specific combinations of growth factors in a serum-free culture medium. The procedure allowed the ex vivo expansion of CD34+ progenitor and stem cells into a pure erythroid precursor population. When injected into nonobese diabetic, severe combined immunodeficient (NOD/SCID) mice, the erythroid cells were capable of proliferation and terminal differentiation into mature enucleated RBCs. The approach may eventually be useful in clinical transfusion applications.

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Figure 1: Large-scale expansion of human erythroid cells.
Figure 2: Analysis of the hemoglobin (Hb) produced by the expanded erythroid cells.
Figure 3: Appearance of CFSE+ human cells in NOD/SCID mice.
Figure 4: Characterization of CFSE+/LDS human RBCs sorted on day 7.
Figure 5: HLA class I and HLA-DR analyses of cells expanded for ten days.

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Acknowledgements

The authors thank B. Drayton, M. Adam, J. Van Nifterik, A. Yapo, R. Gilot, and the cytometry team of Armand Trousseau Hospital for technical assistance, P. Gane for the gift of RhD antibodies, and Y. Brossard, P. Rouyer-Fessard, and Y. Bezard for helpful discussions. We are also grateful to M. Ardouin for the valuable gift of NOD/SCID mice. This work was supported by grants from the Association pour la Recherche en Transfusion, the Etablissement Français des Greffes, and La Ligue Contre le Cancer. T.M.A.N.-N. received a grant from the Association Combattre la Leucémie.

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Correspondence to Luc Douay.

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Neildez-Nguyen, T., Wajcman, H., Marden, M. et al. Human erythroid cells produced ex vivo at large scale differentiate into red blood cells in vivo. Nat Biotechnol 20, 467–472 (2002). https://doi.org/10.1038/nbt0502-467

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