Mesenchymal stem cell-derived small extracellular vesicles facilitate repair of acute obstruction-induced colonic anastomosis injury by modulating early-stage inflammation in rats.

BACKGROUND: Anastomotic leakage (AL), a major complication of colonic anastomoses, leads to prolonged hospital stays and increased mortality. Despite various interventions, AL incidence remains high at approximately 8%. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) have emerged as promising therapeutic agents because of their ability to exert immunoregulatory effects and promote tissue repair. Therefore, in this study, we investigated the role of MSC-sEVs in the healing of colonic anastomoses and elucidated the underlying mechanisms. METHODS: In the preliminary experiments, male Sprague-Dawley rats were assigned to either a colonic obstruction or a sham surgery group, and the impact of acute colonic obstruction on colonic anastomosis healing was assessed, using an anastomotic complication score system. Based on observed impairment in ​healing progression, MSC-sEVs were administered topically in the subsequent experiments, and their therapeutic effects on anastomotic healing were analysed. RESULTS: Acute bowel obstruction impaired colonic anastomosis healing on postoperative day four; however, the topical administration of MSC-sEVs significantly improved healing. This was mainly demonstrated by reduced immune cell infiltration, downregulation of pro-inflammatory pathways, and decreased expression of inflammatory factors, effectively controlling excessive inflammatory responses in early AL healing phases. CONCLUSIONS: In rats, MSC-sEVs effectively improve the healing of acute bowel obstruction-impaired colonic anastomoses during early-phase disease.