Radiotherapy is the second most important treatment modality after surgery in the treatment of cancer. At the present over 50 % of all cancer patients receive radiotherapy at one stage in their course. Inevitably normal tissues are exposed to ionising radiation during radiotherapy of tumours. This can result in organ failure and hence seriously can limit the treatment dose. Reduction of the side effects of radiotherapy will not only increase the quality of life after the treatment but may also result in increased survival of cancer patients as it will allow dose-escalation to the tumour. This is true even if the most optimal physical dose-delivery (conformal therapy, protons) of radiation is applied. Radiation-induced organ failure is mainly caused by stem cell sterilisation, leading to a reduced reconstitution of functional cells. Replenishment of the depleted stem cell compartment should allow regeneration of irradiated tissues. Multipotent stem cells have now been shown to reside in multiple adult tissues. The innovative vision of this project is to reduce radiation-induced complications through stem cell therapy. Hereto, bone marrow derived stem cells will be isolated, mobilised and characterised. Thus obtained stem cells will be tested for their capability to ameliorate radiation-induced complications in organs affected by radiotherapy. After completion of the project (at 24months) the obtained scientific and (bio) technological knowledge and expertise on stem cells and radiation must have established the potential of stem cell therapy to restore normal tissue functioning after irradiation. This should set the stage for the second phase of the project (25-60 months) in which methods are further improved and, importantly, late responding tissues are included. A successful replacement of stem cells and subsequent amelioration of radiation-induced complications may open theroad to completely new strategies in radiotherapy.
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