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Esophageal extracellular matrix hydrogel mitigates metaplastic change in a dog model of Barrett's esophagus.
Science Advances ( IF 11.7 ) Pub Date : 2020-07-01 , DOI: 10.1126/sciadv.aba4526
Juan Diego Naranjo 1, 2 , Lindsey T Saldin 1, 3 , Eric Sobieski 1 , Lina M Quijano 1 , Ryan C Hill 4 , Patrick G Chan 1, 5 , Crisanto Torres 1, 5 , Jenna L Dziki 1, 2 , Madeline C Cramer 1, 3 , Yoojin C Lee 1, 3 , Rohit Das 6 , Anant K Bajwa 1 , Rania Nossair 1 , Molly Klimak 1 , Lucile Marchal 1 , Shil Patel 1 , Sachin S Velankar 1, 7 , Kirk C Hansen 4 , Kevin McGrath 6 , Stephen F Badylak 1, 2, 3
Affiliation  

Chronic inflammatory gastric reflux alters the esophageal microenvironment and induces metaplastic transformation of the epithelium, a precancerous condition termed Barrett’s esophagus (BE). The microenvironmental niche, which includes the extracellular matrix (ECM), substantially influences cell phenotype. ECM harvested from normal porcine esophageal mucosa (eECM) was formulated as a mucoadhesive hydrogel, and shown to largely retain basement membrane and matrix-cell adhesion proteins. Dogs with BE were treated orally with eECM hydrogel and omeprazole (n = 6) or omeprazole alone (n = 2) for 30 days. eECM treatment resolved esophagitis, reverted metaplasia to a normal, squamous epithelium in four of six animals, and downregulated the pro-inflammatory tumor necrosis factor–α+ cell infiltrate compared to control animals. The metaplastic tissue in control animals (n = 2) did not regress. The results suggest that in vivo alteration of the microenvironment with a site-appropriate, mucoadhesive ECM hydrogel can mitigate the inflammatory and metaplastic response in a dog model of BE.



中文翻译:

食管细胞外基质水凝胶减轻巴雷特食管狗模型的化生变化。

慢性炎症性胃反流改变食管微环境并诱导上皮化生转化,这是一种称为巴雷特食管(BE)的癌前病变。包括细胞外基质 (ECM) 在内的微环境生态位极大地影响细胞表型。从正常猪食管粘膜 (eECM) 中采集的 ECM 被配制为粘膜粘附水凝胶,并显示其在很大程度上保留了基底膜和基质细胞粘附蛋白。患有 BE 的狗口服 eECM 水凝胶和奥美拉唑 ( n = 6) 或单独奥美拉唑 ( n = 2) 治疗 30 天。与对照动物相比,eECM 治疗解决了食管炎,使六只动物中的四只化生恢复为正常的鳞状上皮,并下调了促炎性肿瘤坏死因子 -α +细胞浸润。对照动物( n = 2)的化生组织没有消退。结果表明,使用适当部位的粘膜粘附 ECM 水凝胶改变体内微环境可以减轻 BE 狗模型的炎症和化生反应。

更新日期:2020-07-01
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