Method of large-scale erythrocyte production established using erythrocyte progenitor cells with high replication ability derived from iPS cells



"By transducing two genes (c-MYC and BCL-XL) into iPS cells and ES cells, a Kyoto University research team has succeeded in producing erythrocyte progenitor cells with almost unlimited ability to replicate in vitro, which they then differentiated successfully into mature erythrocytes. Although these erythrocytes consisted mostly of fetal-type hemoglobin, they were confirmed to have oxygen-carrying capacity and to have circulatory capacity following transfusion into mice. Going forward, this technology is expected to contribute to a more reliable transfusion system by offering a new option that allows a stable supply of erythrocytes to be produced without depending on the availability of donor blood. 

The research showed that an increase in the expression of the c-MYC gene led to an enhancement of the replication ability of erythrocyte progenitor cells. It was also found that the expression of the BCL-XL gene was higher during the maturation process of erythrocyte progenitor cells than during their replication process. These findings indicate that these genes are important for the maturation of erythrocytes. As the c-MYC gene and BCL-XL gene are present within erythrocyte progenitor cells, methods that make use of them actually mimic the body's own system and can therefore be thought of as safer with a view to future clinical application than the previously developed systems for large-scale erythrocyte production using oncogene-derived from Human papillomavirus that are not normally expressed in the human body. According to rough calculations, the amount of culture medium needed to produce enough erythrocytes for a normal transfusion pack (containing one trillion units) is 1,000 - 2,000 liters when using direct differentiation from undifferentiated iPS cells, whereas 50-100 liters is sufficient with the newly developed method. The same results were achieved with cells placed in frozen storage and then thawed. If a more efficient enucleation method can be established along with a method for generating erythrocytes containing only adult-type hemoglobin, progress will have been made toward a more reliable supply of erythrocytes for transfusion in the future."

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