Emerging diagnostic and treatment approaches in organ and stem cell transplantation

Replacement of diseased organs and cells by healthy tissue is a dream that has partly been realised through progress in transplantation over the last 50 years. However, for transplantation therapy to achieve greater success and on a wider scale, advance is needed in several directions. These include finding supplementary sources of donor tissues and cells that lend themselves for therapy of a larger number of conditions, such as kidney and liver failure, arthritis, diabetes and tooth loss; and a way of ensuring acceptance of the replacement tissue without the need for lifelong drugs that block the immune system. To accelerate progress, experts in basic biology and transplant medicine at King s College London plan to come together in a joint venture with the Medical Research Council, to form the UK s first MRC Centre for Translation of Research in Transplantation. The Centre s mission is to put research in transplantation on a new trajectory to deliver more rapid and effective modes of diagnosis and treatment. The programme of research will apply extensive knowledge of human immunology, stem cell biology, genomics and imaging to develop new areas that will benefit human health. In collaboration with the King s College Centre of Medical Law and Ethics, the MRC Centre will also play a pivotal role in training and education.

The immune system represents a formidable barrier to organ and cell transplantation adding to the problems caused by severe shortage of replacement tissues. We present a co-ordinated and integrated vision for how basic and clinical research can combine at a single centre to provide new diagnostic and therapeutic opportunities that can be applied to the alleviation of human suffering. The premise is that more specific manipulation of the inflammatory and immune systems will increase the number of donor organs that can be used for transplantation, will reduce the number of mid-term graft failures and will lead to minimisation or elimination of pan-immunosuppressive therapies, thus lowering the incidence of related malignancies. The proposed strategies include: (1) development and clinical trial of membrane targeted regulators of the complement and clotting cascades for the pre-treatment of donor organs; (2) investigation and development of clinical-grade cell based therapies to promote long-term graft acceptance without continuous immunosuppressive drugs; (3) development of new imaging methods for visualising and monitoring the activity of innate and adaptive immune systems, initially in pre-clinical models; (4) clinical and experimental evaluation of biomarkers that help to predict and interpret outcomes of transplantation; and (5) strategies for addressing the impact of the immune response in allogeneic stem cell based therapies. Outcome measures will take into account the rates of organ dysfunction due to ischaemia-reperfusion insult and acute rejection crises, annual graft survival rates, indices of chronic rejection, infection rates, clinical tools for measurement of tolerance, specificity and sensitivity of imaging procedures and predictive analysis in large, well-defined patient cohorts. The initial application and exploitation of the research results will take place in the fields of liver, kidney, bone marrow and stem cell-based repair/replacement of tooth and articular cartilage, and later will extend to other organs and tissues. The programme of studies within the Centre will provide a vibrant cross-disciplinary environment in which future leaders of research will acquire essential skills including the confidence to engage public interest in transplantation research and its benefits for patients.