PT - JOURNAL ARTICLE AU - Ying Wang AU - Yongxing Gao AU - Chaoxia He AU - Zhaohui Ye AU - Sharon Gerecht AU - Linzhao Cheng TI - Scalable Production of Human Erythrocytes from Induced Pluripotent Stem Cells AID - 10.1101/050021 DP - 2016 Jan 01 TA - bioRxiv PG - 050021 4099 - http://biorxiv.org/content/early/2016/04/23/050021.short 4100 - http://biorxiv.org/content/early/2016/04/23/050021.full AB - In vitro production of erythrocytes in physiologic numbers from human induced pluripotent stem cells (hiPSCs) holds great promise for improved transfusion medicine and novel cell therapies. We report here, for the first time, a strategy for scalable and xeno-free differentiation of hematopoietic stem/progenitor cells from hiPSCs and subsequent erythrocytes specification, by using stepwise cell culture conditions and by integrating spinner flasks and rocker. This system supported robust and reproducible definitive hematopoietic differentiation of multiple hiPSC lines. We demonstrated an ultra-high yield of up to 4×109 CD235a+ erythrocytes at >98% purity when using a 1-litre spinner flask for suspension culture. Erythrocytes generated from our system can reach a mature stage with red blood cell (RBC) characteristics of enucleation, β-globin protein expression and oxygen-binding ability. The entire process is xeno-free and clinically compliant, allowing future mass production of hiPSC-derived RBCs for transfusion medicine purposes.