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Role of mesenchymal stem cells in the modulation of visceral pain associated with a model of radiation-induced colorectal ulceration

Christelle Durand has defended her thesis on 19th June 2014 at IRSN in Fontenay-aux-Roses.

Document type > *Mémoire/HDR/Thesis

Keywords >

Research Unit > IRSN/PRP-HOM/SRBE/LR2I

Authors > DURAND Christelle

Publication Date > 16/06/2014

Summary

Patients who undergo pelvic radiotherapy may develop significant incidence of undesirable chronic gastrointestinal complications resulting from radiation-induced damages around the tumour. Chronic visceral pain is one of the radiation-induced side effects that greatly affects the quality of life of “cancer survivors”. The lack of effective analgesic treatment highlights the importance of novel and effective therapeutic strategies. In our laboratory, mesenchymal stromal cell (MSC) based approach showed beneficial immunomodulatory and regenerative effects in a rat model of irreversible radiation-induced colonic ulcers. The goal of my work was to assess the relevance of this model to study radiation-induced visceral persistent hypersensitivity and its modulation by MSC treatment. We first demonstrated that this model is associated with long-lasting visceral hypersensitivity and central neuronal sensitization. In this context we showed then that mast cells (MC) are involved in the mechanism of peripheral sensitization. Moreover, we suggested the implication of the neuromediator NO• in the pathophysiology of persistent radiation-induced visceral hypersensitivity. We also suggested that MSC treatment reversed radiation-induced hypersensitivity by a mechanism that in part may involve the modulation of MC activation and/or the decrease in the number of MC and nerve fiber interactions. In addition, MSC treatment reduced the percentage of nitrinergic neurons, increased after irradiation, and restored colonic muscular contractibility. Such processes may promote the therapeutic benefit of MSC observed in our study.

In conclusion, this work provided new insights on the therapeutic benefit of MSC in our study model and a new argument in favour of their use in a future clinical trial to cure abdominopelvic radiotherapy side effects.

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