title: Neuraminidase enhances in vitro expansion of human erythroid progenitors.
abstract: 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. We used a two-step culture model of human cord blood-derived erythroid progenitors in the presence or absence of high-purity neuraminidase, in a serum-free, defined culture medium. Granulocytic and megakaryocytic progenitor cell expansions were also studied. 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. 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.
authors.affiliation: Etablissement Français du Sang Ile-de-France, Créteil, France, IMRB, Inserm U955, équipe 2: Transfusion et maladies du globule rouge, Institut Mondor de Recherche Biomédicale, Créteil, France.
authors.forename: Gwellaouen
authors.initials: G
authors.lastname: Bodivit
authors.affiliation: Etablissement Français du Sang Ile-de-France, Créteil, France, IMRB, Inserm U955, équipe 2: Transfusion et maladies du globule rouge, Institut Mondor de Recherche Biomédicale, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chadebech
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France, 22 Rue Méchain, 75014 Paris, France, CNRS UMR8104, Paris, France, Université Paris Descartes, Sorbonne-Paris-Cité, Paris, France, Inserm U1035, Université Bordeaux, Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vigon
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France, 22 Rue Méchain, 75014 Paris, France, CNRS UMR8104, Paris, France, Université Paris Descartes, Sorbonne-Paris-Cité, Paris, France.
authors.forename: Azzedine
authors.initials: A
authors.lastname: Yacia
authors.affiliation: Etablissement Français du Sang Ile-de-France, Créteil, France, IMRB, Inserm U955, équipe 2: Transfusion et maladies du globule rouge, Institut Mondor de Recherche Biomédicale, Créteil, France, Etablissement Français du Sang Ile-de-France, Hôpital Paul-Brousse, 94800, Villejuif, France.
authors.forename: Nicolas Burin des
authors.initials: NB
authors.lastname: Roziers
authors.affiliation: Etablissement Français du Sang Ile-de-France, Créteil, France, IMRB, Inserm U955, équipe 2: Transfusion et maladies du globule rouge, Institut Mondor de Recherche Biomédicale, Créteil, France, Upec, Université Paris-Est-Créteil, Créteil, France.
authors.forename: France
authors.initials: F
authors.lastname: Pirenne
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France, 22 Rue Méchain, 75014 Paris, France, CNRS UMR8104, Paris, France, Université Paris Descartes, Sorbonne-Paris-Cité, Paris, France, Laboratoire de Recherche d'Hémobiologie Cochin, Hôpital Cochin, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Fichelson
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism* / Q000494:pharmacology; D010641:Phenotype
chemical_list: D018952:Antigens, CD34; D015295:Antigens, Tumor-Associated, Carbohydrate; C016467:Thomsen-Friedenreich antigen; D009439:Neuraminidase