School of Biomedical Engineering, University of Technology Sydney, Sydney, New South Wales, Australia.
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, New South Wales, Australia.
Med Res Rev. 2023 Sep;43(5):1470-1503. doi: 10.1002/med.21956. Epub 2023 Apr 29.
The global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID-19 pandemic witnessed recently, along with increased air pollution and wildfire events, increases the urgency of identifying the most effective therapeutic measures to combat these diseases even further. Despite increasing expenditure and extensive collaborative efforts to identify and develop the most effective and safe treatments, the failure rates of drugs evaluated in human clinical trials are high. To reverse these trends and minimize the cost of drug development, ineffective drug candidates must be eliminated as early as possible by employing new, efficient, and accurate preclinical screening approaches. Animal models have been the mainstay of pulmonary research as they recapitulate the complex physiological processes, Multiorgan interplay, disease phenotypes of disease, and the pharmacokinetic behavior of drugs. Recently, the use of advanced culture technologies such as organoids and lung-on-a-chip models has gained increasing attention because of their potential to reproduce human diseased states and physiology, with clinically relevant responses to drugs and toxins. This review provides an overview of different animal models for studying respiratory diseases and evaluating drugs. We also highlight recent progress in cell culture technologies to advance integrated models and discuss current challenges and present future perspectives.
全球呼吸系统疾病负担巨大，每年都有数百万人因此过早患病和死亡。最近全球发生的 COVID-19 大流行，以及空气污染和野火事件的增加，使得确定最有效治疗这些疾病的措施变得更加紧迫。尽管为了确定和开发最有效和安全的治疗方法而增加了支出并进行了广泛的合作，但在人体临床试验中评估的药物的失败率仍然很高。为了扭转这些趋势并最大限度地降低药物开发成本，必须尽早通过采用新的、高效和准确的临床前筛选方法来淘汰无效的药物候选物。由于能够重现复杂的生理过程、多器官相互作用、疾病表型和药物的药代动力学行为，动物模型一直是肺部研究的基础。最近，由于其在复制人类疾病状态和生理学方面的潜力，以及对药物和毒素的临床相关反应，先进的培养技术，如类器官和肺芯片模型的应用引起了越来越多的关注。本综述介绍了用于研究呼吸系统疾病和评估药物的不同动物模型。我们还强调了细胞培养技术的最新进展，以推进整合模型，并讨论了当前的挑战和未来的前景。
