Institut of Radiation and Nuclear safety, France
Title: Treatment with mesenchymal stem cells (MSC) of lesions induced by accidental irradiation and radiotherapy
Alain Chapel is scientific investigator at IRSN. He has been developing cell therapy to protect against the effects of radiation. He collaborates with clinicians to strategies for treatment of patients after radiation. He has participated in the establishment of proof of concept of the therapeutic efficacy of MSCs. He is a member of national and international societies. He is associate editor of World Journal of Stem Cells, World Journal of Gastrointestinal Surgery, World Journal of Radiology, The Open Gene Therapy Journal and Journal of Clinical Rehabilitative Tissue Engineering Research. He has participated in the scientific organization of international conferences.
The IRSN (Institute for radiation and nuclear safety) is the French National Agency responsible for prevention and treatment of irradiation victims. IRSN group has in the past five years contributed to (i) the understanding of the deleterious effects of therapeutic/accidental radiation on healthy tissues and (ii) their regeneration by MSC therapy. We have developed and tested cell therapy for protection against radiation side effects in several animal models, and we proposed mechanisms to explain the benefit brought by this new therapeutic approach. We established the proof of concept that MSC migrate to damaged tissues in the NOD/SCID immunotolerant mice model and in non-human primates (J Gen Med 2003, Blood 2004, Stem Cells 2006, Br J Radiol 2007). In the NOD/SCID mouse model, we showed that the intravenous injection of MSC (i) sustains haematopoiesis after total body irradiation (Blood 2004), (ii) improves wound healing after radiodermatitis (Annals of Hematology 2006) and (iii) protects gut function from irradiation damages (Adv Exp Med Biol. 2006). Thanks to a tight collaboration with clinicians from several French hospitals (Clinical trials…), we have been the only ones so far able to report successful treatments of therapeutic/accidental radiation damages in several victims with MSC injection. Haematopoiesis correction: In collaboration with Saint-Antoine Hospital (Paris, France), we first reported the haematopoiesis recovery in two patients with Bone Marrow failure (graft failure post grafting and Aplastic Anemia) after intravenous injection of MSC which restored the BM micro-environment, mandatory to sustain haematopoiesis after total body irradiation (Leukemia 2004, 2007). We also treated with the clinical team the first patients over irradiated in Epinal with infusion of MSC, following a specific mission form the ministry of health. Radio-induced burns: Cutaneous reactions are major actors in radiation accidents and a limitation for radiotherapy. In collaboration with Percy hospital (Clamart, France) we have shown for the first time the efficiency of MSC therapy in five patients with acute cutaneous and muscle damages following accidental irradiation delivered at doses and to fields higher than initially planned (Regen Med 2007, Health Phys 2010). Gastrointestinal disorder management: We demonstrated in the rat model that MSC restore gut functions after radiation damages (Cell Death and Differ 2010), through regulation of endogenous epithelial cell homeostasis (Methods Mol Biol, 2012). Four patients were successfully treated for pelvic overdose exposure (IJROBP in press, Cytotherapy in press). Cell therapy combining different sources of adult stem cells (endothelial progenitor, gingival fibroblast) is under investigation and is being tested in preclinical models of radio induced damage (Art Thromb Vasc Biol 2009, Haematologica 2012, Plos One 2012). In parallel, we started analyzing potential side effects after injection (Tissue Cell 2010).