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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>In rats, MSC-sEVs effectively improve the healing of acute bowel obstruction-impaired colonic anastomoses during early-phase disease.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月6日

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  • Zhiwei Dong,
  • Siran Zhou,
  • Xianfeng Xia,
  • Hon-Chi Yip,
  • Kevin Kai-Chung Leung,
  • Melissa Shannon Chan,
  • Philip Wai-Yan Chiu

摘要

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.

Graphical Abstract