Stem Cells and Immunotherapies: Improving Bone Marrow Transplantation Outcomes

"The stem cell that makes all blood cells is known as the haemopoietic or blood forming stem cell. Before birth it circulates in the developing baby’s blood and is found in the blood of the umbilical cord at birth. After birth its main residence is the bone marrow, where it is located in specific areas or niches, the environment of which regulates its survival and abilities to expand and form different types of blood cells, such as red blood cells and platelets. Errors in the genetic code of the blood forming stem cell can lead to this cell becoming cancerous and thence to the development of such diseases as leukaemias. Of the current UK population, around 3 million individuals will develop cancers of the blood and more will be affected by other blood disorders such as the sickle cell disease and thalassaemia. NHSBT plays a key role in treating patients with severe blood disorders, serving a population of ca. 20-30 million individuals in England alone. The Department of Health and NHSBT have had the foresight to invest significant resources in building a network of national specilaised facilities and transplant expertise, in establishing the first public NHS Cord Blood Bank in the UK with a high quality resource of over 14,500 unrelated cord blood units, many from black and ethnic minority groups unable to find a blood stem cell donor, and a registry of over 300,000 unrelated donors. These blood diseases place a severe burden on those affected, often threatening their survival. Using specific treatments to eradicate the diseased stem cells and then replacing these diseased stem cells with normal blood forming stem cells from donors such as umbilical cord blood can be a curative therapy. However, these therapies are not routine and straight forward and are tailored to meet patient needs. In a significant number of cases these therapies will fail and, depending on the disease, 5-10 year survival rates can be poor. Reasons for failure include insufficient blood stem cells in the transplant or graft, inability of these cells to form sufficient functional blood cells once they reach the bone marrow, the reappearance of the disease or of the blood cancer stem cells, attack by the transplanted cells on the recipient’s vital organs when the transplant is not fully matched and infections developing during the treatment. Using the unique resources within NHSBT, we will align our specialist NHSBT expertise with that of our academic colleagues into one programme of research which is close to the patient and which will optimise NHS/NHSBT resources for the benefit of patients in the NHS. We will then take a three pronged approach to improving the outcome for these transplant patients. First we aim to understand how normal blood stem cells reach the bone marrow after they are transplanted and then expand and produce sufficient normal blood cells for a lifetime so that we can optimise blood cell recovery during treatment. Second, we plan to identify and target specific populations of leukaemic stem cells to prevent the reappearance of these cells and the relapse of the patient undergoing these treatments. Third, we will use the body’s own immune cells to prevent incompletely matched transplanted cells from attacking the patient’s organs inappropriately and to fight infections which the patient may contract an develop new methods to ensure better matching of the donor blood stem cells with the patient’s own tissues."