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Large‐Scale Ex Vivo Generation of Human Red Blood Cells from Cord Blood CD34+ Cells
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Large‐Scale Ex Vivo Generation of Human Red Blood Cells from Cord Blood CD34+ Cells
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Journal Article
Large‐Scale Ex Vivo Generation of Human Red Blood Cells from Cord Blood CD34+ Cells
2017
Overview
The ex vivo generation of human red blood cells on a large scale from hematopoietic stem and progenitor cells has been considered as a potential method to overcome blood supply shortages. Here, we report that functional human erythrocytes can be efficiently produced from cord blood (CB) CD34+ cells using a bottle turning device culture system. Safety and efficiency studies were performed in murine and nonhuman primate (NHP) models. With the selected optimized culture conditions, one human CB CD34+ cell could be induced ex vivo to produce up to 200 million erythrocytes with a purity of 90.1% ± 6.2% and 50% ± 5.7% (mean ± SD) for CD235a+ cells and enucleated cells, respectively. The yield of erythrocytes from one CB unit (5 million CD34+ cells) could be, in theory, equivalent to 500 blood transfusion units in clinical application. Moreover, induced human erythrocytes had normal hemoglobin content and could continue to undergo terminal maturation in the murine xenotransplantation model. In NHP model, xenotransplantation of induced human erythrocytes enhanced hematological recovery and ameliorated the hypoxia situation in the primates with hemorrhagic anemia. These findings suggested that the ex vivo‐generated erythrocytes could be an alternative blood source for traditional transfusion products in the clinic. Stem Cells Translational Medicine 2017;6:1698–1709 This study showed an efficient technology for ex vivo generating human erythrocytes. The yield of erythrocytes derived from one cord blood unit (5 million CD34+ cells) could, in theory, be equivalent to 500 blood transfusion units in clinical application. Xenotransfusion studies in mice and nonhuman primates confirmed the safety and efficiency for generated erythrocytes.
Publisher
Oxford University Press,John Wiley and Sons Inc
