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Abstract：
BACKGROUND: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects premature infants. Although mounting evidence supports the therapeutic effect of exosomes on NEC, the underlying mechanisms remain unclear.
OBJECTIVE: To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice.
METHODS: NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.
RESULTS: We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.
CONCLUSIONS: These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.
OBJECTIVE: To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice.
METHODS: NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.
RESULTS: We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.
CONCLUSIONS: These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.
摘要：
背景：坏死性小肠结肠炎（NEC）是一种严重的胃肠道疾病，会影响早产儿。尽管越来越多的证据支持外泌体对NEC的治疗作用，潜在机制尚不清楚.
目的：探讨脐带间充质干细胞(UCMSCs)外泌体调控炎症反应和肠屏障功能的机制,以及它们在缓解新生小鼠NEC方面的潜力。
方法：通过缺氧和灌胃喂养含脂多糖（LPS）的配方，在5天龄的C57BL/6幼崽中诱导NEC，之后,小鼠接受人UCMSC外泌体(hUCMSC-exos)。允许对照小鼠用它们的水母进行母乳喂养。从小鼠收集回肠组织并通过组织病理学和免疫印迹分析。从NEC新生儿中收集结肠组织，并通过免疫荧光进行分析。采用分子生物学和细胞培养方法研究肠上皮细胞的相关机制。
结果：我们发现在NEC过程中肠上皮细胞中自噬过度激活，导致紧密连接蛋白的表达减少和炎症反应增加。hUCMSC-exos在小鼠模型中改善NEC的能力取决于肠自噬的降低。我们还表明，hUCMSC-exos减轻了LPS诱导的肠上皮细胞的炎症反应并增加了迁移能力。
结论：这些结果有助于更好地理解hUCMSC-exos对NEC的保护机制，为NEC的治疗提供新的理论和实验基础。这些发现也增强了我们对自噬机制在NEC中的作用的理解。为确定新的治疗靶点提供了潜在的途径。
目的：探讨脐带间充质干细胞(UCMSCs)外泌体调控炎症反应和肠屏障功能的机制,以及它们在缓解新生小鼠NEC方面的潜力。
方法：通过缺氧和灌胃喂养含脂多糖（LPS）的配方，在5天龄的C57BL/6幼崽中诱导NEC，之后,小鼠接受人UCMSC外泌体(hUCMSC-exos)。允许对照小鼠用它们的水母进行母乳喂养。从小鼠收集回肠组织并通过组织病理学和免疫印迹分析。从NEC新生儿中收集结肠组织，并通过免疫荧光进行分析。采用分子生物学和细胞培养方法研究肠上皮细胞的相关机制。
结果：我们发现在NEC过程中肠上皮细胞中自噬过度激活，导致紧密连接蛋白的表达减少和炎症反应增加。hUCMSC-exos在小鼠模型中改善NEC的能力取决于肠自噬的降低。我们还表明，hUCMSC-exos减轻了LPS诱导的肠上皮细胞的炎症反应并增加了迁移能力。
结论：这些结果有助于更好地理解hUCMSC-exos对NEC的保护机制，为NEC的治疗提供新的理论和实验基础。这些发现也增强了我们对自噬机制在NEC中的作用的理解。为确定新的治疗靶点提供了潜在的途径。
