PSC-RED, an Albumin-Free Robust Erythroid Differentiation Method to Produce Enucleated Red Blood Cells from Human Pluripotent Stem Cells

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.