Mesothelial Cell Recruitment Towards Sites of Post-Surgical Adhesion Formation in the Peritoneal Cavity

Abstract Background Abdominal surgeries are often inevitable and live-saving procedures, however, they can be associated with post-surgical complications, such as the formation of irreversible scar bands called peritoneal adhesions. Adhesions in the peritoneal cavity can lead to serious health burden by causing small bowel obstruction, infertility, and chronic pelvic pain. Unfortunately, no effective treatment for adhesion patients exists today. Mesothelial cells and mesothelial cell-derived mesenchymal myofibroblasts have been identified as key players in the pathogenesis of adhesions, and thus represent a novel target for pharmacological interventions. Aims Our aim is to study the molecular mechanisms of mesothelial cell recruitment towards peritoneal adhesion sites, which could serve as potential drug targets to effectively prevent the formation of adhesions. Methods By exploiting genetic lineage tracing and experimental animal surgery, we have established a surgical-transgenic mouse model system that allows us to study mesothelial cell recruitment during processes of scar-free wound healing and wound healing associated with adhesion formation. To identify candidate molecules predominantly required for the recruitment of mesothelial cells towards adhesion sites, we apply an untargeted transcriptomics-based research strategy (spatial transcriptomics, single cell RNA sequencing). Results Histological characterization of our mouse model showed that over seven days post-surgery increasing numbers of mesothelial or mesothelial cell-derived cells accumulate at adhesion sites whereas their numbers stay constant in wounds healing without scar formation. Along with these findings, we have determined candidate molecules potentially triggering mesothelial cell migration towards sites of adhesion formation and will next test their proposed function in vivo and in vitro. Conclusions Mesothelial cells and mesothelial cell-derived mesenchymal myofibroblasts particularly accumulate at sites of adhesion formation. Therapeutic targeting of the recruitment mechanism of these cells might represent a novel strategy to prevent post-surgical adhesion formation in the peritoneal cavity.