Publication: Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics
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2021-09-10
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23290501
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2-s2.0-85120067694
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Mahidol University
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Molecular Therapy - Methods and Clinical Development. Vol.22, (2021), 26-39
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Deborah E. Daniels, Daniel C.J. Ferguson, Rebecca E. Griffiths, Kongtana Trakarnsanga, Nicola Cogan, Katherine A. MacInnes, Kathryn E. Mordue, Tatyana Andrienko, Ivan Ferrer-Vicens, Daniel Ramos Jiménez, Phillip A. Lewis, Marieangela C. Wilson, Maurice A. Canham, Ryo Kurita, Yukio Nakamura, David J. Anstee, Jan Frayne (2021). Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/76026.
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Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics
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Author(s)
Deborah E. Daniels
Daniel C.J. Ferguson
Rebecca E. Griffiths
Kongtana Trakarnsanga
Nicola Cogan
Katherine A. MacInnes
Kathryn E. Mordue
Tatyana Andrienko
Ivan Ferrer-Vicens
Daniel Ramos Jiménez
Phillip A. Lewis
Marieangela C. Wilson
Maurice A. Canham
Ryo Kurita
Yukio Nakamura
David J. Anstee
Jan Frayne
Daniel C.J. Ferguson
Rebecca E. Griffiths
Kongtana Trakarnsanga
Nicola Cogan
Katherine A. MacInnes
Kathryn E. Mordue
Tatyana Andrienko
Ivan Ferrer-Vicens
Daniel Ramos Jiménez
Phillip A. Lewis
Marieangela C. Wilson
Maurice A. Canham
Ryo Kurita
Yukio Nakamura
David J. Anstee
Jan Frayne
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Abstract
Developing 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.