Screening Therapeutic Effects of MSC-EVs to Acute Lung Injury Model on A Chip.

Abstract

Acute lung injury (ALI) is a lethal disease with high mortality rate, and its physiologically relevant models that could mimic human disease processes are urgently needed to study pathophysiology and predict drug efficacy. Here, this work presents a novel lipopolysaccharide(LPS) based ALI model on a microfluidic chip that reconstitutes an air-liquid interface lined by human alveolar epithelium and microvascular endothelium for screening the therapeutic effects of mesenchymal stem cells (MSC) derived extracellular vesicles (MSC-EVs) to the biomimetic ALI. The air-liquid interface is established by coculture of alveolar epithelium and microvascular endothelium on the opposite sides of the porous membrane. The functionalized architecture is characterized by integrate cell layers and suitable permeability. Using this biomimetic microsystem, LPS based ALI model is established, which exhibits the disrupted alveolar-capillary barrier, reduced transepithelial/transendothelial electrical resistance (TEER), and impaired expression of junction proteins. As a reliable disease model, this work examines the effects of MSC-EVs, and the data indicate the therapeutic potential of EVs for severe ALI. MSC-EVs can alleviate barrier disruption by restoring both the epithelial and endothelial barrier integrity. They hope this study can become a unique approach to study human pathophysiology of ALI and advance drug development.