Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics

dc.contributor.authorDeborah E. Danielsen_US
dc.contributor.authorDaniel C.J. Fergusonen_US
dc.contributor.authorRebecca E. Griffithsen_US
dc.contributor.authorKongtana Trakarnsangaen_US
dc.contributor.authorNicola Coganen_US
dc.contributor.authorKatherine A. MacInnesen_US
dc.contributor.authorKathryn E. Mordueen_US
dc.contributor.authorTatyana Andrienkoen_US
dc.contributor.authorIvan Ferrer-Vicensen_US
dc.contributor.authorDaniel Ramos Jiménezen_US
dc.contributor.authorPhillip A. Lewisen_US
dc.contributor.authorMarieangela C. Wilsonen_US
dc.contributor.authorMaurice A. Canhamen_US
dc.contributor.authorRyo Kuritaen_US
dc.contributor.authorYukio Nakamuraen_US
dc.contributor.authorDavid J. Ansteeen_US
dc.contributor.authorJan Frayneen_US
dc.contributor.otherJapanese Red Cross Societyen_US
dc.contributor.otherSiriraj Hospitalen_US
dc.contributor.otherNHS Blood and Transplanten_US
dc.contributor.otherRiken BioResource Research Centeren_US
dc.contributor.otherScottish National Blood Transfusion Serviceen_US
dc.contributor.otherUniversity of Bristolen_US
dc.contributor.otherAustralian Red Cross Lifeblooden_US
dc.description.abstractDeveloping robust methodology for the sustainable production of red blood cells in vitro is essential for providing an alternative source of clinical-quality blood, particularly for individuals with rare blood group phenotypes. Immortalized erythroid progenitor cell lines are the most promising emergent technology for achieving this goal. We previously created the erythroid cell line BEL-A from bone marrow CD34+ cells that had improved differentiation and enucleation potential compared to other lines reported. In this study we show that our immortalization approach is reproducible for erythroid cells differentiated from bone marrow and also from far more accessible peripheral and cord blood CD34+ cells, consistently generating lines with similar improved erythroid performance. Extensive characterization of the lines shows them to accurately recapitulate their primary cell equivalents and provides a molecular signature for immortalization. In addition, we show that only cells at a specific stage of erythropoiesis, predominantly proerythroblasts, are amenable to immortalization. Our methodology provides a step forward in the drive for a sustainable supply of red cells for clinical use and for the generation of model cellular systems for the study of erythropoiesis in health and disease, with the added benefit of an indefinite expansion window for manipulation of molecular targets.en_US
dc.identifier.citationMolecular Therapy - Methods and Clinical Development. Vol.22, (2021), 26-39en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleReproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeuticsen_US