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

TL;DR

This study shows that mesenchymal stem cell-derived small extracellular vesicles can improve healing of colonic anastomoses impaired by acute obstruction in rats.

Contribution

The novel finding is that MSC-sEVs reduce inflammation and promote healing in early stages of colonic anastomosis injury.

Findings

MSC-sEVs significantly improved healing of colonic anastomoses impaired by acute obstruction.

MSC-sEVs reduced immune cell infiltration and downregulated pro-inflammatory pathways.

MSC-sEVs decreased expression of inflammatory factors in early healing phases.

Abstract

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.

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.

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.

In rats, MSC-sEVs effectively improve the healing of acute bowel obstruction-impaired colonic anastomoses during early-phase disease.

The online version contains supplementary material available at 10.1186/s13287-025-04551-8.

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