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

Autor: David J. Anstee, Phillip A. Lewis, Daniel Ramos Jiménez, Tatyana N Andrienko, Kathryn E. Mordue, Deborah E. Daniels, Marieangela C. Wilson, Ivan Ferrer-Vicens, Yukio Nakamura, Rebecca E. Griffiths, Daniel C. J. Ferguson, Ryo Kurita, Maurice A. Canham, Kongtana Trakarnsanga, Nicola Cogan, Jan Frayne, Katherine A. MacInnes
Rok vydání: 2021
Předmět:
Zdroj: Molecular Therapy: Methods & Clinical Development, Vol 22, Iss, Pp 26-39 (2021)
Daniels, D, Ferguson, D C J, Trakarnsanga, T, Cogan, N M, MacInnes, K, Andrienko, T N, Ferrer Vicens, I, Wilson, M C, Anstee, D J & Frayne, J 2021, ' Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics ', Molecular Therapy-Methods and Clinical Development, vol. 22, pp. 26-39 . https://doi.org/10.1016/j.omtm.2021.06.002
Molecular Therapy. Methods & Clinical Development
ISSN: 2329-0501
DOI: 10.1016/j.omtm.2021.06.002
Popis: 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.
Graphical abstract
Here Daniels et al. demonstrate reproducible immortalization of erythroid cells derived from bone marrow and peripheral and cord blood CD34+ cells and reveal a molecular signature of immortalization. This methodology provides a step toward the sustainable production of red cells for clinical use and for the generation of cellular model systems.
Databáze: OpenAIRE