Differentiation of human pluripotent stem cells for red blood cell production

The clinical demand for blood transfusions remains high, especially for patients with rare blood groups in need of urgent care. Red blood cells (RBCs) are the most frequently transfused blood component, with 2 million donated RBC units required in the UK every year (Lawes 2011), which costs £309 million. The production of a personalized blood cell product for emergency or rare blood type transfusions is being investigated to alleviate clinical dependence on blood donation (Douay and Andreu 2007). Currently, RBCs can be generated in vitro from human hematopoietic stem/progenitor cells (HSCs) of umbilical cord blood (UCB), bone marrow (BM), mobilized peripheral blood (PB) or from pluripotent stem cells (hPSCs), where hPSCs possess unlimited self-renewal potentially allowing for unlimited HSC and RBC generation. This chapter summarizes the state of the art of ex vivo culture conditions: methodology and culture system(s) for producing erythroid cells from hPSCs, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). In particular, the chapter discusses the most prominent issues that need to be addressed to facilitate translation into a clinical grade product.