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Development and Application of a Functional Human Esophageal Mucosa Explant Platform to Eosinophilic Esophagitis
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Development and Application of a Functional Human Esophageal Mucosa Explant Platform to Eosinophilic Esophagitis
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Journal Article
Development and Application of a Functional Human Esophageal Mucosa Explant Platform to Eosinophilic Esophagitis
2019
Overview
There is an increasing prevalence of esophageal diseases but intact human tissue platforms to study esophageal function, disease mechanisms, and the interactions between cell types
in situ
are lacking. To address this, we utilized full thickness human donor esophagi to create and validate the
ex vivo
function of mucosa and smooth muscle (n = 25). Explanted tissue was tested for contractile responses to carbachol and histamine. We then treated
ex vivo
human esophageal mucosa with a cytokine cocktail to closely mimic the Th2 and inflammatory milieu of eosinophilic esophagitis (EoE) and assessed alterations in smooth muscle and extracellular matrix function and stiffening. We found that full thickness human esophagus as well as the individual layers of circular and longitudinal muscularis propria developed tension in response to carbachol
ex vivo
and that mucosa demonstrated squamous cell differentiation. Treatment of mucosa with Th2 and fibrotic cytokines recapitulated the majority of the clinical Eosinophilic Esophagitis Diagnostic Profile (EDP) on fluidic transcriptional microarray. Transforming growth factor-beta-1 (TGFβ1) increased gene expression of fibronectin, smooth muscle actin, and phospholamban (p < 0.001). The EoE cocktail also increased stiffness and decreased mucosal compliance, akin to the functional alterations in EoE (p = 0.001). This work establishes a new, transcriptionally intact and physiologically functional human platform to model esophageal tissue responses in EoE.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/107
/ 14/1
/ 14/63
/ 38/77
/ 692/420
/ Actin
/ Eosinophilic Esophagitis - diagnosis
/ Eosinophilic Esophagitis - immunology
/ Eosinophilic Esophagitis - pathology
/ Esophageal Mucosa - drug effects
/ Esophageal Mucosa - pathology
/ Extracellular Matrix - drug effects
/ Gene Expression - drug effects
/ Humanities and Social Sciences
/ Humans
/ Mucosa
/ Muscle, Smooth - drug effects
/ Science
