Dong Zhiwei, Zhou Siran, Xia Xianfeng, Yip Hon-Chi, Leung Kevin Kai-Chung, Chan Melissa Shannon, Chiu Philip Wai-Yan
Division of Upper Gastro-intestinal and Metabolic Surgery, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, N.T, China.
Department of Endoscopy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Stem Cell Res Ther. 2025 Aug 6;16(1):433. doi: 10.1186/s13287-025-04551-8.
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.
吻合口漏（AL）是结肠吻合术的主要并发症，会导致住院时间延长和死亡率增加。尽管采取了各种干预措施，AL的发生率仍高达约8%。间充质干细胞衍生的小细胞外囊泡（MSCs-sEVs）因其具有免疫调节作用和促进组织修复的能力，已成为有前景的治疗剂。因此，在本研究中，我们研究了MSCs-sEVs在结肠吻合口愈合中的作用，并阐明了其潜在机制。
在初步实验中，将雄性Sprague-Dawley大鼠分为结肠梗阻组或假手术组，使用吻合口并发症评分系统评估急性结肠梗阻对结肠吻合口愈合的影响。基于观察到的愈合进程受损情况，在后续实验中局部给予MSCs-sEVs，并分析其对吻合口愈合的治疗效果。
急性肠梗阻在术后第4天损害了结肠吻合口愈合；然而，局部给予MSCs-sEVs显著改善了愈合情况。这主要表现为免疫细胞浸润减少、促炎途径下调以及炎症因子表达降低，有效控制了AL早期愈合阶段的过度炎症反应。
在大鼠中，MSCs-sEVs在疾病早期能有效改善急性肠梗阻受损的结肠吻合口愈合情况。
