Esophageal extracellular matrix hydrogel mitigates metaplastic change in a dog model of Barrett's esophagus.

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

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.