title: Superior survival ofex vivocultured human reticulocytes following transfusion into mice.
abstract: The generation of cultured red blood cells from stem cell sources may fill an unmet clinical need for transfusion-dependent patients, particularly in countries that lack a sufficient and safe blood supply. Cultured red blood cells were generated from human CD34+cells from adult peripheral blood or cord blood byex vivoexpansion, and a comprehensivein vivosurvival comparison with standard red cell concentrates was undertaken. Significant amplification (>105-fold) was achieved using CD34+cells from both cord blood and peripheral blood, generating high yields of enucleated cultured red blood cells. Following transfusion, higher levels of cultured red cells could be detected in the murine circulation compared to standard adult red cells. The proportions of cultured blood cells from cord or peripheral blood sources remained high 24 hours post-transfusion (82±5% and 78±9%, respectively), while standard adult blood cells declined rapidly to only 49±9% by this time. In addition, the survival time of cultured blood cells in mice was longer than that of standard adult red cells. A paired comparison of cultured blood cells and standard adult red blood cells from the same donor confirmed the enhancedin vivosurvival capacity of the cultured cells. The study herein represents the first demonstration thatex vivogenerated cultured red blood cells survive longer than donor red cells using anin vivomodel that more closely mimics clinical transfusion. Cultured red blood cells may offer advantages for transfusion-dependent patients by reducing the number of transfusions required.
authors.affiliation: NIHR Blood and Transplant Research Unit, Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, UK.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kupzig
authors.affiliation: NIHR Blood and Transplant Research Unit, Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, UK.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Parsons
authors.affiliation: Statistics and Clinical Studies, National Health Service Blood and Transplant, Bristol, UK.
authors.forename: Elinor
authors.initials: E
authors.lastname: Curnow
authors.affiliation: NIHR Blood and Transplant Research Unit, Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Anstee
authors.affiliation: NIHR Blood and Transplant Research Unit, Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, UK allison.blair@bristol.ac.uk.|School of Cellular and Molecular Medicine, University of Bristol, UK.
authors.forename: Allison
authors.initials: A
authors.lastname: Blair
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D016913:Blood Component Transfusion; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D057899:Cytophagocytosis; D004912:Erythrocytes / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008264:Macrophages; D051379:Mice; D010641:Phenotype; D012156:Reticulocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34