Engineering ‘die on demand’ cells to treat Graft-versus-Host Disease What is this research looking at? A stem cell or bone marrow transplant replaces damaged blood cells with healthy ones. It can be used to treat conditions affecting the blood cells, such as leukaemia and lymphoma. At present, bone marrow transplantation is the only curative treatment for many blood cancers, but its use can be marred by Graft-versus-Host Disease (GvHD). GvHD is a possible complication of a stem cell transplant. It is when patients receive stem cells from a non-relative, called a donor or an allogeneic transplant that there is a risk of GvHD. GvHD means the donor's stem cells (known as graft) react against the patient’s own cells (the host). Unfortunately, GvHD still have high mortality in those patients who do not respond to conventional therapies. Among the therapies for GvHD, the use of a small population of cells – mesenchymal stem cells (MSC) – is very promising. However, we still do not know how to fully exploit all the potentials of these cells. With my research we have now discovered that MSC are curative only when they die after being transfused and the patients who do not respond are those not able to kill MSC. With this project, I will engineer MSC able to reach the GvHD target organs first and, once there, to die “on demand”. This strategy will be a tailored treatment which overcome the need for the patient to kill the cells and will make the treatment effective in virtually all patients. What could this mean for people affected by leukaemia? Transplant is the only curative therapy for most leukaemia patients; however, its success is limited by graft versus host disease (GvHD). Effective treatment and management of GvHD will translate into a higher possibility of successful transplant (and then cure) for most patients with leukaemia.