Open Access

ARTICLE

Neuraminidase enhances in vitro expansion of human erythroid progenitors

Gwellaouen Bodivit^1,2, Philippe Chadebech^1,2, Isabelle Vigon^4,5,6,8, Azzedine Yacia^4,5,6, Nicolas Burin des Roziers^1,2,9, France Pirenne^1,2,3,a, Serge Fichelson^4,5,6,7,a

1 Etablissement Franc¸ais du Sang Ile-de-France, Créteil, France
2 IMRB, Inserm U955, équipe 2: Transfusion et maladies du globule rouge, Institut Mondor de Recherche Biomédicale, Créteil, France
3 Upec, Université Paris-Est-Créteil, Créteil, France
4 Inserm U1016, Institut Cochin, Paris, France, 22 Rue Méchain, 75014 Paris, France
5 CNRS UMR8104, Paris, France
6 Université Paris Descartes, Sorbonne-Paris-Cité, Paris, France
7 Laboratoire de Recherche d’Hémobiologie Cochin, Hôpital Cochin, Paris, France
8 Inserm U1035, Université Bordeaux, Bordeaux, France
9 Etablissement Franc¸ais du Sang Ile-de-France, Hôpital Paul-Brousse, 94800, Villejuif, France
a FP and SF contributed equally to this work.

* Corresponding Author: Serge Fichelson, sergefi

European Cytokine Network 2016, 27(2), 23-33. https://doi.org/10.1684/ecn.2016.0374

Abstract

Background: In spite of recent key improvements, in vitro mass production of erythrocytes from human stem cells is still limited by difficulties in obtaining sufficient numbers of erythroid progenitors. In fact, such progenitors are as scarce in the bone marrow as in peripheral blood. Study design and Methods: We used a two-step culture model of human cord blood-derived erythroid progenitors in the presence or absence of highpurity neuraminidase, in a serum-free, defined culture medium. Granulocytic and megakaryocytic progenitor cell expansions were also studied. Results: We show that significant enhancement of erythroid cell generation is obtained when CD34+ human hematopoietic progenitors are cultured in the presence of neuraminidase. Interestingly, in so doing, expanded red cell progenitors remained erythropoietin-dependent for further expansion and survival, and cells thus generated displayed a normal phenotype. Moreover, the activity of neuraminidase on these cells can be reversed by simple cell washing. Finally, growth of cells of the other myeloid lineages (granulocytes and megakaryocytes) is either decreased or unchanged in the presence of neuraminidase. Conclusion: This specific feature of neuraminidase, that of stimulation of human red cell progenitor proliferation, provides a safe technique for producing greater numbers of in vitro-generated red blood cells for both basic research and transfusion use.

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Keywords

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