Abstract

Cultured red blood cells (cRBCs) have many potential applications in transfusion medicine and drug delivery. We report that we have developed chemically defined, albumin-free Robust Erythroid Differentiation (RED) methods to produce enucleated cRBCs from human induced pluripotent stem cells (iPSCs). Human iPSC-derived cRBCs produced with either the short or long variation of the RED protocol respectively express embryonic/fetal or a mixture of fetal and adult hemoglobins. The long version of the protocol produces up to 50% of enucleated cells at an unprecedented yield. RED is scalable and relies on inexpensive components and therefore dramatically increases the feasibility and economic viability of all translational applications of cRBCs.\n\nHighlightsO_LIPSC-RED: A chemically-defined, albumin-free Robust Erythroid Differentiation (RED) methods to produce cRBCs from human induced pluripotent stem cells.\nC_LIO_LIPSC-RED produces up to 50% enucleated cells at an unprecedented yield.\nC_LIO_LIPSC-RED is scalable and relies on inexpensive components and therefore increases the feasibility and economic viability of translational applications of cRBCs.\nC_LI