title: Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.
abstract: Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.
authors.affiliation: Laboratory of Cellular Hematology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Sandeep N
authors.initials: SN
authors.lastname: Shah
authors.affiliation: Laboratory of Cellular Hematology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Monique P
authors.initials: MP
authors.lastname: Gelderman
authors.affiliation: Laboratory of Cellular Hematology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Emily M A
authors.initials: EM
authors.lastname: Lewis
authors.affiliation: Laboratory of Cellular Hematology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Farrel
authors.affiliation: Laboratory of Biochemistry and Vascular Biology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Francine
authors.initials: F
authors.lastname: Wood
authors.affiliation: Laboratory of Biochemistry and Vascular Biology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Michael Brad
authors.initials: MB
authors.lastname: Strader
authors.affiliation: Laboratory of Biochemistry and Vascular Biology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Abdu I
authors.initials: AI
authors.lastname: Alayash
authors.affiliation: Laboratory of Cellular Hematology, Division of Hematology Research and Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Jaroslav G
authors.initials: JG
authors.lastname: Vostal
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001803:Blood Transfusion / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010100:Oxygen / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D010100:Oxygen