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Biotechnol J. 2014 Jan;9(1):28-38. doi: 10.1002/biot.201200368. Epub 2013 Oct 23.

Large-scale production of red blood cells from stem cells: what are the technical challenges ahead?

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UPMC University Paris 6, UMR_S938, Proliferation and Differentiation of Stem Cells, Paris, France; INSERM, UMR_S938, Proliferation and Differentiation of Stem Cells, Paris, France; Université Paris Diderot, Paris, France.


Blood-transfusion centers regularly face the challenge of donor blood shortages, especially for rare blood groups. The possibility of producing universal red blood cells from stem cells industrially has become a possible alternative since the successful injection of blood generated in vitro into a human being in 2011. Although there remains many biological and regulatory issues concerning the efficacy and safety of this new product, the major challenge today for future clinical applications is switching from the current limited 2-dimensional production techniques to large-scale 3-dimensional bioreactors. In addition to requiring technological breakthroughs, the whole process also has to become at least five-fold more cost-efficient to match the current prices of high-quality blood products. The current review sums up the main biological advances of the past decade, outlines the key biotechnological challenges for the large-scale cost-effective production of red blood cells, proposes solutions based on strategies used in the bioindustry and presents the state-of-the-art of large-scale blood production.


Bioreactors; Clinical applications; Cost-effectiveness; Hematopoietic stem cells; Red blood cells

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