4.7 Article

Human ex vivo lung perfusion: a novel model to study human lung diseases

Journal

SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41598-020-79434-4

Keywords

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Funding

  1. VMI-University ofPittsburgh
  2. Pulmonary Fibrosis Foundation
  3. [R01 HL123766-04]
  4. [P30CA047904]

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The study suggests that EVLP of diseased human lungs is suitable for translational research on chronic lung diseases. By perfusing the lungs for 6 hours with EVLP, researchers were able to assess airway mechanics, pulmonary hemodynamics, gas exchange, and biochemical parameters continuously. Tissue biopsies were also collected to isolate RNA and DNA for identifying unique gene expressions of different diseases, demonstrating the utility of EVLP as a relevant experimental model for understanding pulmonary pathophysiology and various human lung diseases.
Experimental animal models to predict physiological responses to injury and stress in humans have inherent limitations. Therefore, the development of preclinical human models is of paramount importance. Ex vivo lung perfusion (EVLP) has typically been used to recondition donor lungs before transplantation. However, this technique has recently advanced into a model to emulate lung mechanics and physiology during injury. In the present study, we propose that the EVLP of diseased human lungs is a well-suited preclinical model for translational research on chronic lung diseases. Throughout this paper, we demonstrate this technique's feasibility in pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), emphysema, and non-disease donor lungs not suitable for transplantation. In this study, we aimed to perfuse the lungs for 6 h with the EVLP system. This facilitated a robust and continuous assessment of airway mechanics, pulmonary hemodynamics, gas exchange, and biochemical parameters. We then collected at different time points tissue biopsies of lung parenchyma to isolate RNA and DNA to identify each disease's unique gene expression. Thus, demonstrating that EVLP could successfully serve as a clinically relevant experimental model to derive essential insights into pulmonary pathophysiology and various human lung diseases.

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