Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, W1244 BST Tower, 200 Lothrop Street, Pittsburgh, PA, 15261, USA.
Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sci Rep. 2021 Jan 12;11(1):490. doi: 10.1038/s41598-020-79434-4.
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.
用于预测人类损伤和应激生理反应的实验动物模型存在固有局限性。因此，开发临床前人体模型至关重要。离体肺灌注（EVLP）通常用于在移植前对供肺进行再处理。然而，这项技术最近已经发展成为一种模拟损伤期间肺力学和生理学的模型。在本研究中，我们提出，对患病人体肺进行 EVLP 是一种适合慢性肺部疾病转化研究的临床前模型。在整篇论文中，我们证明了该技术在肺动脉高压（PAH）、特发性肺纤维化（IPF）、肺气肿和不适合移植的非疾病供体肺中的可行性。在这项研究中，我们的目标是使用 EVLP 系统对肺进行 6 小时灌注。这有助于对气道力学、肺血液动力学、气体交换和生化参数进行稳健和连续的评估。然后，我们在不同的时间点采集肺实质的组织活检，以分离 RNA 和 DNA，以确定每种疾病独特的基因表达。因此，证明 EVLP 可以成功用作临床相关的实验模型，为了解肺部病理生理学和各种人类肺部疾病提供重要的见解。
