Department of General Pediatrics and Neonatology, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Feulgenstrasse 12, 35392 Giessen, Germany.
Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center (UGMLC), Cardiopulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Aulweg 130, 35392 Giessen, Germany.
Int J Mol Sci. 2021 Jan 24;22(3):1138. doi: 10.3390/ijms22031138.
Bronchopulmonary dysplasia (BPD) remains one of the most devastating consequences of preterm birth resulting in life-long restrictions in lung function. Distorted lung development is caused by its inflammatory response which is mainly provoked by mechanical ventilation, oxygen toxicity and bacterial infections. Dysfunction of resident lung mesenchymal stem cells (MSC) represents one key hallmark that drives BPD pathology. Despite all progress in the understanding of pathomechanisms, therapeutics to prevent or treat BPD are to date restricted to a few drugs. The limited therapeutic efficacy of established drugs can be explained by the fact that they fail to concurrently tackle the broad spectrum of disease driving mechanisms and by the huge overlap between distorted signal pathways of lung development and inflammation. The great enthusiasm about MSC based therapies as novel therapeutic for BPD arises from the capacity to inhibit inflammation while simultaneously promoting lung development and repair. Preclinical studies, mainly performed in rodents, raise hopes that there will be finally a broadly acting, efficient therapy at hand to prevent or treat BPD. Our narrative review gives a comprehensive overview on preclinical achievements, results from first early phase clinical studies and challenges to a successful translation into the clinical setting.
支气管肺发育不良（BPD）仍然是早产儿最严重的后果之一，导致肺功能终身受限。肺发育畸形是由其炎症反应引起的，主要由机械通气、氧毒性和细菌感染引起。驻留肺间充质干细胞（MSC）功能障碍是驱动 BPD 病理的一个关键标志。尽管在了解发病机制方面取得了所有进展，但预防或治疗 BPD 的治疗方法迄今为止仅限于少数几种药物。已建立的药物的有限治疗效果可以解释为它们未能同时解决广泛的疾病驱动机制，以及肺发育和炎症的扭曲信号通路之间存在巨大重叠。基于 MSC 的治疗作为 BPD 的新型治疗方法引起了极大的关注，因为它具有抑制炎症的能力，同时促进肺发育和修复。主要在啮齿动物中进行的临床前研究，让人们希望最终将有一种广泛作用、有效的治疗方法用于预防或治疗 BPD。我们的叙述性综述全面概述了临床前研究的成果、早期临床研究的结果以及成功转化为临床环境所面临的挑战。
