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Cell therapy for the treatment of accidental radiation overexposure

DRPH, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PO Box 17, 92262 Fontenay-aux-Roses, France

Irradiation kills cells directly or indirectly, and the basic issue is to replace them. To do so, the cells required to heal the injured compartment can be obtained from a non- (or less) injured part of the body or from an allogeneic source. Because the number of cells necessary to treat an injury can be very high, the cells have to be expanded ex vivo. Owing to their transdifferentiation or plasticity property, cells from some tissues could even possibly repopulate another system. Human bone marrow contains two cell compartments: the haematopoietic cell compartment, and the stromal cell compartment that comprises mesenchymal stem cells (MSCs). Both compartments could be used for cell therapy. We will focus on four specific questions. Is it possible to use ex vivo expansion of haematopoietic cells to treat bone marrow aplasia? Are human MSCs homing in the injured tissues following irradiation? Is it possible to separate MSC haematopoietic support from MSC homing ability following irradiation? Is it possible to combine haematopoietic cells and MSCs to treat a radiation-induced multi-organ failure syndrome? To study these points, we have developed an irradiated NOD/SCID mouse model for human cell transplantation, and a non-human primate model for large field irradiation. Our results suggest that cell therapy could be a valuable approach for the treatment of multiple organ failure.