Throughout the last decades, radiotherapy established as a major tool in the treatment of abdominopelvic cancers. Despite great technological evolutions, radiotherapy remains associated with side effects that can sometimes be really harmful, this being mainly due to the toxicity of ionizing radiations for healthy tissues surrounding the tumor. As part of abdominopelvic radiotherapies, these side effects mainly affect the gastrointestinal tract, which is very sensitive to radiations. The development of curative treatments thus became a priority. Mesenchymal stem cells (MSC) showed their immunomodulatory ability as well as their ability to regenerate tissue in many models. During my thesis, we aimed at giving rise to the therapeutic advantage brought by MSC in the treatment of radioinduced damage as well as the underlying molecular mechanisms. Our results allowed us to demonstrate the efficiency of our treatment with an effect both on the colic epithelial structure and on its contractile functions. We demonstrated that this therapeutical efficiency depends on two processes. Stimulation of the epithelial proliferation through the Wnt pathway allows the epithelial regeneration process to be enhanced. The increased local corticosterone secretion allows the number and the activation state of T lymphocytes to diminish. Our results moreover suggest the existence of a link between the two observed phenomenons thus providing with a new proof of the combinatory effects of MSC therapy.
Treatment of radio-induced colorectal lesions with Mesenchymal Stromal Cells (MSC) : part of the inflamatory process