Erythropoiesis in Health and Disease

"Blood for transfusion saves lives and is precious to the NHS. Erythropoiesis or making red blood cells is not only fundamental to human health and more specifically to the health of blood donors but also becomes abnormal in many patients requiring blood products. This programme will improve the health of blood donors and the blood supply by systematically analysing the published data, advancing our understanding on the basis of iron deficiency in blood donors and suggest how this may be predicted and prevented. It is now possible to grow red blood cells from a variety of cells including precursor or immature cells found in the umbilical cord of newborns and more remarkably from blood cells derived from adult skin cells. We will optimise the ability of these cells to make red blood cells and in doing so will be able to grow red blood cells from defined individuals with valuable blood types for helping to test blood groups and cross-match blood. Recapitulating the last phases of growth of red blood cells is surprisingly less well understood but we have developed the tools to understand how the final discoid red blood cells that circulate in our blood vessels are produced. We will optimise red cell production in the laboratory and see how these cells differ from red blood cells taken for transfusion. The early or mature red blood cells grown in the laboratory may be tested as new types of blood transfusion or replacement in the future. Finally, we will study a large group of patients who have lost the ability to make red blood cells normally and often become transfusion dependent. We will study why their bone marrow cells are unable to make red blood cells and see if we can define groups of patients whose disease is less serious than others and/or respond to treatment. This personalised or tailored approach to the definition of disease type and therapy promises more effective and cost-effective treatment in the future. This programme has been designed to study these issues in the context of the population of England & Wales and the impact of changes in practice to patients, the National Blood Service and the NHS: • What research evidence do we already have on iron deficiency in donors? • Why do some blood donors become iron deficient and how can we predict this? • What cells can we use to grow red blood cells in the laboratory? • Can we make large amounts of red blood cells in the laboratory? • Why can’t some people make enough red blood cells? • Can we predict which patients will respond to treatment? The work will be done by a large group of doctors and researchers across the NHS and Universities of Liverpool, Oxford and London over a five year period. The outputs of the programme may have a significant impact on the health of blood donors and patients and provide individualised and possibly more effective treatment for transfusion dependent patients with bone marrow disorders"