University of Minnesota Masonic Children's Hospital, Department of Pediatrics,, Minneapolis, Minnesota.
Pediatr Res. 2018 Jan;83(1-2):308-317. doi: 10.1038/pr.2017.237. Epub 2017 Oct 25.
Advances in neonatal medicine have led to increased survival of infants born at the limits of viability, resulting in an increased incidence of bronchopulmonary dysplasia (BPD). BPD is a chronic lung disease of premature infants characterized by the arrest of alveolarization, fibroblast activation, and inflammation. BPD leads to significant morbidity and mortality in the neonatal period and is one of the leading causes of chronic lung disease in children. The past decade has brought a surge of trials investigating cellular therapies for the treatment of pulmonary diseases. Mesenchymal stem cells (MSCs) are of particular interest because of their ease of isolation, low immunogenicity, and anti-inflammatory and reparative properties. Clinical trials of MSCs have demonstrated short-term safety and tolerability; however, studies have also shown populations of MSCs with adverse pro-inflammatory and myofibroblastic characteristics. Cell-based therapies may represent the next breakthrough therapy for the treatment of BPD, however, there remain barriers to implementation as well as gaps in knowledge of the role of endogenous MSCs in the pathogenesis of BPD. Concurrent high-quality basic science, translational, and clinical studies investigating the fundamental pathophysiology underlying BPD, therapeutic mechanisms of exogenous MSCs, and logistics of translating cellular therapies will be important areas of future research.
新生儿医学的进步导致了能够在生存极限出生的婴儿存活率的增加,从而导致支气管肺发育不良(BPD)的发病率增加。BPD 是一种早产儿的慢性肺部疾病,其特征是肺泡化、成纤维细胞激活和炎症的停止。BPD 在新生儿期导致显著的发病率和死亡率,是儿童慢性肺部疾病的主要原因之一。过去十年中,针对细胞疗法治疗肺部疾病的试验数量激增。间充质干细胞(MSCs)因其易于分离、低免疫原性以及抗炎和修复特性而备受关注。MSCs 的临床试验已经证明了短期的安全性和耐受性;然而,研究也表明 MSCs 群体具有不良的促炎和肌成纤维特性。基于细胞的疗法可能代表着治疗 BPD 的下一个突破性治疗方法,但是,在实施方面仍然存在障碍,并且对 BPD 发病机制中内源性 MSCs 的作用的了解也存在差距。同时进行高质量的基础科学、转化和临床研究,以调查 BPD 的基本病理生理学、外源性 MSCs 的治疗机制以及细胞疗法的转化,将是未来研究的重要领域。