title: An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells.
abstract: With increasing worldwide demand for safe blood, there is much interest in generating red blood cells in vitro as an alternative clinical product. However, available methods for in vitro generation of red cells from adult and cord blood progenitors do not yet provide a sustainable supply, and current systems using pluripotent stem cells as progenitors do not generate viable red cells. We have taken an alternative approach, immortalizing early adult erythroblasts generating a stable line, which provides a continuous supply of red cells. The immortalized cells differentiate efficiently into mature, functional reticulocytes that can be isolated by filtration. Extensive characterization has not revealed any differences between these reticulocytes and in vitro-cultured adult reticulocytes functionally or at the molecular level, and importantly no aberrant protein expression. We demonstrate a feasible approach to the manufacture of red cells for clinical use from in vitro culture.
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.|Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Kongtana
authors.initials: K
authors.lastname: Trakarnsanga
authors.affiliation: Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol BS34 7QH, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Rebecca E
authors.identifier: 0000-0001-7461-0635
authors.initials: RE
authors.lastname: Griffiths
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Marieangela C
authors.initials: MC
authors.lastname: Wilson
authors.affiliation: Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol BS34 7QH, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.|School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Allison
authors.initials: A
authors.lastname: Blair
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Satchwell
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Meinders
authors.affiliation: Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol BS34 7QH, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cogan
authors.affiliation: Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol BS34 7QH, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kupzig
authors.affiliation: Department of Research and Development, Central Blood Institute, Japanese Red Cross Society, Tokyo 135-8521, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kurita
authors.affiliation: Cell Engineering Division, RIKEN BioResource Center, Ibaraki 305-0074, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.|Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol BS34 7QH, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Toye
authors.affiliation: Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Bristol BS34 7QH, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Anstee
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.|NIHR Blood and Transplant Research Unit, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Frayne
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D004900:Erythroblasts / Q000166:cytology* / Q000378:metabolism; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D005240:Feasibility Studies; D006801:Humans; D066298:In Vitro Techniques; D012156:Reticulocytes / Q000166:cytology* / Q000378:metabolism