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In vitro engineering of human cartilage: a preclinical model relevant to exposition of surrounding healthy tissues during radiotherapy
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Edité par CCSD -
International audience. The ARCHADE project (Advanced Resource Centre for HADrontherapy in Europe) will erect in Caen within few years a resource center of research and development for hadrontherapy with carbon ions and a cancer treatment facility by protontherapy. Hadrontherapy concists to treat relevant cancers with unconventional radiations (hadrons) in order to deliver a significant dose to the tumor with harmlessness impact to surrounding healthy tissues. This technology is a promising tool for treatment of resistant tumors to conventional low linear energy transfer (LET) radiotherapy (X-rays). The benefit of better ballistic and high efficiency of carbon ions (Relative Biological Efficiency, RBE of 2-3) for cancer treatment was demonstrated since a decade.However, if the better ballistic of protontherapy is already successfully used worldwide,hadrontherapy with carbon ions stay underused and raise some concerns about likely side effects for patients. During the last decade, Hadronbiology studies have most focused on signaling and repair of DNA damage pathways induced by ionizing radiation in immortalized cells under conditions dramatically different of human homeostasis. Thus, this research needs to be broadened as the range of normal tissue responses to ionizing radiation are still not fully understood even though it is recognized that these responses are the major limiting factor in the rupture of tissue homeostasis after therapeutic exposure. By using relevant tissue models as cartilage, we aim at unveiling the impact of acute radiations on cells fate and function. We then implement cartilage3D culture system to study the effects of irradiation on the differentiation/proliferation balance, viability, genetic stability, oxidative stress, inflammation of chondrosarcoma and human primary chondrocytes. Indeed, since one decade, 3D models are used in radiobiology to approach tissue physiology. However, vascular damages have recently been show to play an important role in tissue response to radiation exposure. Except for cartilage, which is the only avascular tissue of human body, all 3D models available are develop without vascular compartment and, per se, have key restraint in their use as relevant model for radiobiology.
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