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Transfusion therapies involving red blood cells (RBCs), platelets, and neutrophils depend on the donation of these cells from healthy volunteers. However, unpredictable adverse results can ensue from transfusion therapies because of the donation of cells from a very large number of anonymous volunteers. For example, transfusion of blood products that include hazardous viruses or prions is difficult to prevent completely because, occasionally, tests to detect them yield pseudo-negative results. This comment is, of course, not intended as a criticism of the current system that is dependent on volunteers who act as blood donors from their own good will. However, there is little doubt that RBCs, platelets, and neutrophils produced in vitro might be a preferable means of producing such cells, thereby reducing, or even eliminating, the need for a large pool of anonymous donors. To date, however, the use of hematopoietic cells produced in vitro has not proved practical for routine therapeutic applications. RBC transfusion was the first transplantation procedure to be established and is now routine and indispensable for many clinical purposes. However, in many countries the supply of transfusable materials is not always sufficient. In Japan, for example, the supply of RBCs with an AB/RhD(-) phenotype is always lacking because individuals with this RBC phenotype are rare. This problem of inequalities in the supply and demand for RBCs has stimulated interest in the development of in vitro procedures for the generation of transfusable and functional RBCs from hematopoietic stem cells or progenitor cells present in bone marrow or umbilical cord blood (Figure 1) (Neildez-Nguyen et al., 2002; Giarratana et al., 2005; Miharada et al., 2006; Douay and Andreu, 2007). In addition, it is important to realize that clinical risk factors associated with RBC transfusions have not been entirely excluded. One notable and very severe complication of the procedure can be transfusion-related acute lung injury (TRALI), which has only recently been recognized and has not yet been eliminated (Silliman et al., 2009; Looney et al., 2010). One of the possible causes of TRALI may be a factor in the transfused materials, such as antibodies in the transfused materials against antigens on the leukocytes. This type of adverse outcome also results from the dependence of blood transfusion on the supply of blood from a large number of anonymous individuals. Problems may arise if donated blood is utilized without sufficient preliminary trials being carried out on each sample. The use of RBCs derived from selected human resources may help to alleviate these problems, since they can be intensively tested for pathogens before clinical use. Trial transfusions of a minimal amount of material into each

ES Cell-derived Erythroid Cell Lines Able to Produce Mature Red Blood Cells