Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Cell Death Dis. 2020 Sep 14;11(9):750. doi: 10.1038/s41419-020-02964-2.
Necrotizing enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society. The treatment and the outcome of the disease have not changed in recent decades. Emerging evidence has shown that stimulating the Wnt/β-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment. Amniotic fluid stem cells (AFSC) and AFSC-derived extracellular vesicles (EV) can be used to improve intestinal injury in experimental NEC. However, the mechanisms by which they affect the Wnt/β-catenin pathway and intestinal regeneration are unknown. In our current study, we demonstrated that AFSC and EV attenuate NEC intestinal injury by activating the Wnt signaling pathway. AFSC and EV stimulate intestinal recovery from NEC by increasing cellular proliferation, reducing inflammation and ultimately regenerating a normal intestinal epithelium. EV administration has a rescuing effect on intestinal injury when given during NEC induction; however, it failed to prevent injury when given prior to NEC induction. AFSC-derived EV administration is thus a potential emergent novel treatment strategy for NEC.
坏死性小肠结肠炎（NEC）是一种严重的肠道疾病，主要影响早产儿，给家庭和社会带来高发病率、高死亡率和巨大的经济负担。近几十年来，该疾病的治疗方法和预后并未发生改变。新出现的证据表明，刺激 Wnt/β-连环蛋白通路和增强肠道再生在实验性 NEC 中是有益的，这可能成为一种新的治疗方法。羊水干细胞（AFSC）和 AFSC 衍生的细胞外囊泡（EV）可用于改善实验性 NEC 中的肠道损伤。然而，它们影响 Wnt/β-连环蛋白通路和肠道再生的机制尚不清楚。在我们目前的研究中，我们证明 AFSC 和 EV 通过激活 Wnt 信号通路来减轻 NEC 肠道损伤。AFSC 和 EV 通过增加细胞增殖、减少炎症，最终再生正常的肠上皮，来刺激 NEC 后肠道的恢复。在 NEC 诱导期间给予 EV 治疗具有肠损伤的挽救作用；然而，在 NEC 诱导前给予 EV 治疗则不能预防损伤。因此，AFSC 衍生的 EV 给药可能是一种治疗 NEC 的潜在新策略。
