Lesage Flore, Jimenez Julio, Toelen Jaan, Deprest Jan
a Department of Development and Regeneration, Group Biomedical Sciences , KU Leuven , Leuven , Belgium.
b Department of Obstetrics and Gynaecology , Clínica Alemana Universidad del Desarrollo , Santiago , Chile.
J Matern Fetal Neonatal Med. 2018 Apr;31(7):958-966. doi: 10.1080/14767058.2017.1301927. Epub 2017 Mar 21.
Bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity as no effective treatment is available to date. This calls for the exploration of new therapeutic options like cell therapy, which is already effective for various human (lung) disorders. We systematically searched the MEDLINE, Embase, and Web of Science databases from the earliest date till January 2017 and included original studies on the perinatal use of cell-based therapies (i.e. cells and/or cell-derivatives) to treat BDP in animal models. Fourth publications describing 47 interventions were retrieved. Newborn mice/rats raised in a hyperoxic environment were studied in most interventions. Different cell types - either intact cells or their conditioned medium - were administered, but bone marrow and umbilical cord blood derived mesenchymal stem cells were most prevalent. All studies reported positive effects on outcome parameters including alveolar and vascular morphometry, lung function, and inflammation. Cell homing to the lungs was demonstrated in some studies, but the therapeutic effects seemed to be mostly mediated via paracrine modulation of inflammation, fibrosis and angiogenesis.
Multiple rat/mouse studies show promise for cell therapy for BPD. Yet careful study of action mechanisms and side effects in large animal models is imperative before clinical translation can be achieved.
支气管肺发育不良(BPD)仍然是极早产儿最常见的并发症,因为迄今为止尚无有效的治疗方法。这就需要探索新的治疗选择,如细胞疗法,该疗法已对各种人类(肺部)疾病有效。我们系统检索了MEDLINE、Embase和Web of Science数据库,时间跨度从最早到2017年1月,纳入了关于围产期使用基于细胞的疗法(即细胞和/或细胞衍生物)治疗动物模型中BPD的原始研究。检索到47项干预措施的4篇相关文献。大多数干预措施研究的是在高氧环境中饲养的新生小鼠/大鼠。使用了不同类型的细胞——完整细胞或其条件培养基,但骨髓和脐带血来源的间充质干细胞最为常见。所有研究均报告了对包括肺泡和血管形态测量、肺功能及炎症在内的结局参数有积极影响。一些研究证实细胞归巢至肺部,但治疗效果似乎主要是通过对炎症、纤维化和血管生成的旁分泌调节介导的。
多项大鼠/小鼠研究显示细胞疗法对BPD有前景。然而,在实现临床转化之前,必须在大型动物模型中仔细研究作用机制和副作用。