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

Autor: Naranjo JD; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA., Saldin LT; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA., Sobieski E; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Quijano LM; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Hill RC; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Chan PG; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Cardiothoracic Surgery, UPMC, Pittsburgh, PA 15213, USA., Torres C; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Cardiothoracic Surgery, UPMC, Pittsburgh, PA 15213, USA., Dziki JL; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA., Cramer MC; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA., Lee YC; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA., Das R; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, UPMC, Pittsburgh, PA 15213, USA., Bajwa AK; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Nossair R; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Klimak M; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Marchal L; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Patel S; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA., Velankar SS; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Chemical Engineering, Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261, USA., Hansen KC; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., McGrath K; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, UPMC, Pittsburgh, PA 15213, USA., Badylak SF; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2020 Jul 01; Vol. 6 (27), pp. eaba4526. Date of Electronic Publication: 2020 Jul 01 (Print Publication: 2020).
DOI: 10.1126/sciadv.aba4526
Abstrakt: 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.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
Databáze: MEDLINE