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Immortalization of erythroid progenitors for in vitro large-scale red cell production

Abstract : Population ageing and increase in cancer incidence may lead to a decreased availability of red blood cell units. Thus, finding an alternative source of red blood cells is a highly relevant challenge. The possibility to reproduce in vitro the human erythropoiesis opens a new era, particularly since the improvement in the culture systems allows to produce erythrocytes from induced-Pluripotent Stem Cells (iPSCs), or CD34(+) Hematopoietic Stem Cells (HSCs). iPSCs have the advantage of in vitro self-renewal, but lead to poor amplification and maturation defects (high persistence of nucleated erythroid precursors). Erythroid differentiation from HSC allows a far better amplification and adult-like hemoglobin synthesis. But the inability of these progenitors to self-renew in vitro remains a limit in their use as a source of stem cells. A major improvement would consist in immortalizing these erythroid progenitors so that they could expand indefinitively. Inducible transgenesis is the first way to achieve this goal. To date, the best immortalized-cell models involve strong oncogenes induction, such as c-Myc, Bcl-xL, and mostly E6/E7 HPV16 viral oncoproteins. However, the quality of terminal differentiation of erythroid progenitors generated by these,oncogenes is not optimal yet and the long-term stability of such systems is unknown. Moreover, viral transgenesis and inducible expression of oncogenes raise important problems in term of safety, since the enucleation rate is not 100% and no nucleated cells having replicative capacities should be present in the final product. (C) 2017 Elsevier Masson SAS. All rights reserved.
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Soumis le : vendredi 11 mars 2022 - 11:14:12
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A. Caulier, L. Guyonneau Harmand, Loic Garcon. Immortalization of erythroid progenitors for in vitro large-scale red cell production. Transfusion Clinique et Biologique, Elsevier, 2017, 24 (3), pp.263-267. ⟨10.1016/j.tracli.2017.06.030⟩. ⟨hal-03605646⟩



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