Large-Scale Ex Vivo Generation of Human Red Blood Cells from Cord Blood CD34+ Cells

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.