Exploring the activation and intercommunication mechanisms of mesenchymal stromal cells within chronic pathological settings ; Étude des mécanismes d’activation et de communication des cellules stromales mésenchymateuses en contexte pathologique chronique

Mesenchymal stromal cells (MSC) are pluripotent cells, located in a quiescent state, in perivascular and perineural niches of virtually all adult tissues. Recent findings have described a pivotal and multifaceted role of MSC in the inflammatory response. Indeed, in response to tissue injury, MSC activation leads to the acquisition of various functions, such as immunomodulation, trophicity and differential potential, that contribute to tissue repair. In chronic inflammation, MSCs are involved in fibrosis formation and in tumor progression, by their ability to differentiate into myofibroblasts and cancer-associated fibroblasts, respectively. This doctoral work aims to investigate the mechanisms involved in the activation of MSC. This evaluation is mostly based on the characterization of the CD248 expression, a marker of MSC, in an autoimmune (rheumatoid arthritis) and a tumoral context (colorectal cancer). Furthermore, this work evaluates the role of the anaphylatoxin C3a (and its receptor, C3aR) in MSC communication with the tumor microenvironment, particularly in glioblastoma. Additionally, this work discusses the ability of MSCs to transform into tumor cells in the context of glioblastoma. The results of this work argue for an essential role of MSCs in chronic diseases and describe complex mechanisms involving CD248 in the regulation and activation of MSCs and the C3a/C3aR axis in communication with the tumor microenvironment. Thus, these results provide a better understanding of the pathogenesis of chronic diseases, including cancer, and open up important prospects for fundamental, clinical, and therapeutic research in these oftenconsidered irreversible diseases. ; Les cellules stromales mésenchymateuses (MSC) sont des cellules pluripotentes, de localisation périvasculaire et périnerveuse, présentes dans la majorité des tissus à un stade quiescent à l’âge adulte. Les données scientifiques récentes ont montré un rôle clé de ces cellules au sein de la réaction inflammatoire grâce à leurs propriétés multiples. En ...