Efecto inmunomodulador de las células endometriales estromales procedentes de sangre menstrual en distintos modelos murinos de inflamación

Résumé

In this dissertation, we assessed the impact that MenSCs administration had in two mouse models of acute inflammation: a thioglycollate (TGC)-elicited peritonitis model and the Salmonella Typhimurium sepsis model. We found that in the TGC model, MenSCs intraperitoneal injection altered the local recruitment of macrophages, neutrophils and other innate immune cells. Moreover, this variation in the number and percentage of peritoneal populations was dependent on MenSCs administration timepoint. MenSCs administered at the onset of macrophage recruitment migrated to distant organs and promoted, locally, the formation of peritoneal aggregates. These aggregates harboured macrophages, neutrophils and the injected MenSCs. In vitro, the stimulation of MenSCs with TGC altered their expression profile enhancing the transcription of both chemoattracting and antiinflammatory mediators. In the Salmonella sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of injection and prevented bacterial clearance. Additional in vitro studies confirmed that co-culture of MenSCs with human macrophages reshaped their phenotype and impaired their bactericidal properties, affecting macrophage bacterial killing and the production of reactive oxygen intermediates. In conclusion, our findings highlight that MenSCs maintain a crosstalk with the physiologic environment, where their impact might modulate phenotypic and functional properties of innate immune populations —primarily macrophages—. Given the influence of the latter in the inflammatory context, MenSCs effects over macrophages must be taken into consideration when aiming to translate MenSCs to a clinical setting. On the other hand, the experimental models first described in this study are elegant work tools to analyse distinct aspects of MenSCs effects, and in general of MSCs, on specific severe pathologies