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

Juan Diego Naranjo, Lindsey T. Saldi, Eric Sobieski, Lina M. Quijan, Ryan C. Hil, Patrick G. Cha, Crisanto Torres, Jenna L. Dzik, Madeline C. Crame, Yoojin C. Le, Rohit Das, Anant K. Bajw, Rania Nossair, Molly Klimak, Lucile Marchal, Shil Patel, Sachin S. Velanka, Kirk C. Hanse, Kevin McGrath, Stephen F. Badyl

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbereaba4526
JournalScience Advances
Volume6
Issue number27
DOIs
StatePublished - Jul 2020
Externally publishedYes

ASJC Scopus subject areas

  • General

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