Naranjo Juan Diego, Saldin Lindsey T, Sobieski Eric, Quijano Lina M, Hill Ryan C, Chan Patrick G, Torres Crisanto, Dziki Jenna L, Cramer Madeline C, Lee Yoojin C, Das Rohit, Bajwa Anant K, Nossair Rania, Klimak Molly, Marchal Lucile, Patel Shil, Velankar Sachin S, Hansen Kirk C, McGrath Kevin, Badylak Stephen F
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Sci Adv. 2020 Jul 1;6(27):eaba4526. doi: 10.1126/sciadv.aba4526. eCollection 2020 Jul.
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 ( = 6) or omeprazole alone ( = 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 ( = 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.
慢性炎症性胃反流会改变食管微环境，并诱导上皮细胞发生化生转化，这是一种被称为巴雷特食管（BE）的癌前病变状态。包括细胞外基质（ECM）在内的微环境生态位对细胞表型有重大影响。从正常猪食管黏膜中提取的ECM（eECM）被制成一种黏膜黏附水凝胶，并显示其在很大程度上保留了基底膜和基质-细胞黏附蛋白。对患有BE的犬口服给予eECM水凝胶和奥美拉唑（ = 6）或仅给予奥美拉唑（ = 2），持续30天。与对照动物相比，eECM治疗缓解了食管炎，使6只动物中的4只动物的化生逆转至正常鳞状上皮，并下调了促炎性肿瘤坏死因子-α细胞浸润。对照动物（ = 2）的化生组织未消退。结果表明，在BE犬模型中，使用适合部位的黏膜黏附ECM水凝胶对微环境进行体内改变可减轻炎症和化生反应。
