Department of Pediatrics, University of Connecticut Health Center, Farmington, 06106 CT, USA.
Department of Pediatrics, University of Connecticut Health Center, Farmington, 06106 CT, USA
Dis Model Mech. 2021 Feb 23;14(2):dmm047753. doi: 10.1242/dmm.047753.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by exposure to high levels of oxygen (hyperoxia) and is the most common complication that affects preterm newborns. At present, there is no cure for BPD. Infants can recover from BPD; however, they will suffer from significant morbidity into adulthood in the form of neurodevelopmental impairment, asthma and emphysematous changes of the lung. The development of hyperoxia-induced lung injury models in small and large animals to test potential treatments for BPD has shown some success, yet a lack of standardization in approaches and methods makes clinical translation difficult. models have also been developed to investigate the molecular pathways altered during BPD and to address the pitfalls associated with animal models. Preclinical studies have investigated the efficacy of stem cell-based therapies to improve lung morphology after damage. However, variability regarding the type of animal model and duration of hyperoxia to elicit damage exists in the literature. These models should be further developed and standardized, to cover the degree and duration of hyperoxia, type of animal model, and lung injury endpoint, to improve their translational relevance. The purpose of this Review is to highlight concerns associated with current animal models of hyperoxia-induced BPD and to show the potential of models to complement studies in the significant improvement to our understanding of BPD pathogenesis and treatment. The status of current stem cell therapies for treatment of BPD is also discussed. We offer suggestions to optimize models and therapeutic modalities for treatment of hyperoxia-induced lung damage in order to advance the standardization of procedures for clinical translation.
支气管肺发育不良（BPD）是一种由暴露于高浓度氧气（高氧）引起的慢性肺部疾病，是影响早产儿的最常见并发症。目前，BPD 尚无治愈方法。婴儿可以从 BPD 中康复；然而，他们会在成年后出现显著的发病率，表现为神经发育障碍、哮喘和肺气肿肺部变化。在小动物和大动物中开发高氧诱导的肺损伤模型以测试 BPD 的潜在治疗方法已取得一些成功，但方法和途径缺乏标准化，使得临床转化困难。还开发了模型来研究 BPD 期间改变的分子途径，并解决与动物模型相关的陷阱。临床前研究已经研究了基于干细胞的疗法在损伤后改善肺形态的功效。然而，文献中存在关于诱发损伤的动物模型类型和高氧持续时间的可变性。这些模型应进一步开发和标准化，以涵盖高氧的程度和持续时间、动物模型的类型和肺损伤终点，以提高其转化相关性。本综述的目的是强调与高氧诱导的 BPD 目前动物模型相关的问题，并展示模型的潜力，以补充研究，从而显著提高我们对 BPD 发病机制和治疗的理解。还讨论了目前用于治疗 BPD 的干细胞疗法的现状。我们提供了优化模型和治疗方式以治疗高氧诱导的肺损伤的建议，以推进临床转化程序的标准化。
