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Modeling lung endothelial dysfunction in sepsis-associated ARDS using a microphysiological system.

Nai-Wen Liang1, Carole Wilson2, Brooke Davis3

  • 1Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, USA.

Physiological Reports
|July 9, 2024
PubMed
Summary
This summary is machine-generated.

Microphysiological systems (MPS) reveal how sepsis patient plasma damages lung endothelial cells, contributing to acute respiratory distress syndrome (ARDS). This model offers a new way to study ARDS mechanisms and find targeted therapies.

Keywords:
ARDSendothelial dysfunctionmicrophysiological systemsepsis

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Area of Science:

  • Pulmonary Medicine
  • Critical Care Medicine
  • Biomedical Engineering

Background:

  • Endothelial dysfunction is a key factor in acute respiratory distress syndrome (ARDS) severity and outcomes.
  • Existing preclinical models often fail to translate to human therapies due to biological differences.
  • Microphysiological systems (MPS) offer a promising platform to study human lung endothelial responses.

Purpose of the Study:

  • To investigate the impact of sepsis patient plasma on lung endothelial cells using an MPS.
  • To identify specific mechanisms of endothelial dysfunction in sepsis-induced ARDS.
  • To establish MPS as a tool for developing targeted ARDS therapies.

Main Methods:

  • Utilized a lung endothelial microphysiological system (MPS).
  • Assessed endothelial permeability, adhesion molecule expression (ICAM-1), and cytokine secretion (IL-6) after exposure to plasma from sepsis patients and healthy controls.
  • Compared responses between sepsis patients with and without ARDS.

Main Results:

  • Sepsis plasma significantly worsened endothelial barrier function, causing cell contraction and defects.
  • Incubation with sepsis plasma increased endothelial ICAM-1 expression and IL-6 secretion compared to healthy plasma.
  • Plasma from sepsis patients who developed ARDS showed heightened IL-6 and soluble ICAM-1 levels.

Conclusions:

  • Lung endothelial MPS can effectively model sepsis-induced endothelial dysfunction relevant to ARDS.
  • This platform allows for the interrogation of specific mechanisms driving ARDS.
  • MPS show potential for identifying and testing novel therapeutic targets for ARDS in sepsis patients.