Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis.,Cell Death & Disease

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Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-09-14 , DOI: 10.1038/s41419-020-02964-2
Bo Li _{1,

2} , Carol Lee _{1,

2} , Joshua S O'Connell _{1,

2} , Lina Antounians _{2,

3} , Niloofar Ganji _{1,

2} , Mashriq Alganabi _{1,

2} , Marissa Cadete _{1,

2} , Francesca Nascimben _{1,

2} , Yuhki Koike _{1,

2} , Alison Hock _{1,

2} , Steven R Botts ₄ , Richard Y Wu ₄ , Hiromu Miyake _{1,

2} , Adam Minich _{1,

2} , Michael F Maalouf _{1,

2} , Elke Zani-Ruttenstock _{1,

2} , Yong Chen _{1,

2} , Kathene C Johnson-Henry ₄ , Paolo De Coppi ₅ , Simon Eaton ₅ , Pekka Maattanen ₆ , Paul Delgado Olguin _{1,

7,

8} , Augusto Zani _{2,

3} , Philip M Sherman _{4,

9,

10,

11} , Agostino Pierro _{1,

2,

12}

Affiliation

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.
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Cell Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Biology Department, Burman University, Lacombe, AB, T4L 2E5, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Heart & Stroke Richard Lewar Centre of Excellence, Toronto, ON, M5S 3H2, Canada.
Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada.
Department of Surgery, University of Toronto, Toronto, ON, M5S 1A8, Canada.

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.

中文翻译：

羊水干细胞来源的细胞外囊泡激活 Wnt 信号可减轻实验性坏死性小肠结肠炎的肠道损伤。

坏死性小肠结肠炎（NEC）是一种破坏性肠道疾病，主要影响早产儿，导致高发病率、高死亡率，给家庭和社会带来巨大损失。近几十年来，这种疾病的治疗方法和结果没有改变。新的证据表明，刺激 Wnt/β-catenin 通路和增强肠道再生对于实验性 NEC 是有益的，并且它们有可能用作一种新的治疗方法。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-catenin 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、减少炎症并最终再生正常肠上皮来刺激 NEC 肠道恢复。在 NEC 诱导期间给予 EV 对肠道损伤具有挽救作用；然而，在 NEC 诱导之前给予它并不能预防损伤。因此，AFSC 衍生的 EV 给药是 NEC 的一种潜在的新兴治疗策略。

更新日期：2020-09-14

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