Red blood cells from pluripotent stem cells for use in transfusion On first consideration, the generation of red blood cells (RBCs) for transfusion from pluripotent stem cells (PSCs) would seem to be unnecessary owing to the excellent provision of donated blood services in many countries. However, although blood transfusion remains an essential mainstay of medical practice there are a number of issues that need to be addressed to ensure sufficient and safe blood supplies for the future. The history of transfusion & the need for a new supply Modern transfusion medicine is mainly built upon the work of the Edinburgh-based physi- cians James Blundell and John Leacock. In the early 19th century, John Leacock demonstrated that experimentally exsanguinated dogs could be resuscitated by transfusing them with blood from other dogs and he suggested in his dissertation of 1817 that this technique could be used for humans [1] . His work was extended by his contemporary, James Blundell, who transfused the first patients with human blood in 1818 [2,3] . A number of important steps in the development of RBC trans- fusion as a routine therapy followed, including the identification of blood groups [4], the development of anticoagulant solutions [5,6] and the develop- ment of screening for microbiological agents [7] . However, RBC transfusion remains problematic in several important respects.  Supply One of the main issues is sufficiency of sup- ply, which is a challenge at times in developed countries, but can be a very serious problem in other parts of the world due to a lack of infra- structure to support widespread nonremuner- ated donation. In Europe and the USA, around 30 million units of RBC concentrate are trans- fused to around 6 million patients, with a total population of around 700 million, giving a rate of 30–50 donations per 1000 population [8,9] . Currently, only 4% of the eligible population donate and there are significant seasonal varia- tions in supply levels with particular shortages in the mid-summer and around Christmas holi- days in the UK. In other countries the situation is much more serious. For example, in Africa last year just 4.2 million units were collected in a total of 27 countries, giving a donation rate of just 6.9 donations per 1000 [201] . Not only do developing countries have the largest problems with supply, they also have the heaviest burden of disease and greatest requirements for blood. For example, worldwide, 150,000 women die each year from postpartum hemorrhage, many or most of whom could be saved by an adequate blood supply.  Transfusion-transmitted infections The transmission of viruses by blood transfusion is well recognized and over the past few decades severe outbreaks of transfusion-transmitted hepa- titis B virus, HIV and hepatitis C virus [7] have garnered much publicity. However, bacterial con- tamination from the skin or blood of the donor remains the most common transfusion-trans- mitted infection overall [10] . Methods are being The use of donated red blood cells in transfusion is a well-established cellular therapy. However, problems including insufficient supply, transfusion-transmitted infections and the need for immunological matching hamper even in the best services. These issues may be eliminated by using pluripotent stem cells to generate universal donor group O, Rhesus D-negative red blood cells. Human embryonic stem cells can be maintained and expanded indefinitely and can, therefore, produce the very large cell numbers required for this application. Red blood cell production is also an attractive goal for pluripotent stem cell-derived therapeutics because it is a well-characterized single cell suspension, lacking nucleated cells and with a low expression of HLA molecules. Much progress has been made; however, a number of challenges remain including scale-up, clinical effectiveness and product safety. KEYWORDS: blood transfusion  cell therapy  current good manufacturing practice  pluripotent stem cell  red blood cell Joanne C Mounord †1,2 , Emmanuel Olivier 1 , Niove E Jordanides 1,2 , Paul de Sousa 3 & Marc L Turner 2,3 1 Faculty of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK 2 Scosh Naonal Blood Transfusion Service Cell Therapy Group, Royal Infirmary Edinburgh, 51 Lile France Cresent, Edinburgh, E16 4SA, UK 3 MRC Centre for Regenerave Medicine, University of Edinburgh, Royal Infirmary Edinburgh, 51 Lile France Crescent, Edinburgh E16 4SA, UK † Author for correspondence: Tel.: +44 141 330 7212 Fax: +44 141 330 5481 j.mounord@bio.gla.ac.uk 411 Review ISSN 1746-0751 10.2217/RME.10.22 © 2010 Future Medicine Ltd Regen. Med. (2010) 5(3), 411–423 For reprint orders, please contact: reprints@futuremedicine.com