Namba Fumihiko
Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
Pediatr Int. 2019 Oct;61(10):945-950. doi: 10.1111/ped.14001. Epub 2019 Oct 14.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants who have been treated with supplemental oxygen and mechanical ventilation. Despite major advances in perinatal and neonatal medicine, limited progress has been made in reducing BPD rates. The use of mesenchymal stem cells (MSC) is a promising and innovative therapy for several diseases because they are easy to extract and they have low immunogenicity, anti-inflammatory properties, and regenerative ability. According to several pre-clinical studies that have used BPD animal models, one mechanism of action for MSC in BPD is mainly due to the paracrine effects of MSC-derived humoral factors, such as interleukin (IL)-6, IL-8, vascular endothelial growth factor, collagen, and elastin, rather than the multilineage and regenerative capacities of MSC. Cell-free preparations derived from MSC, including conditioned media and exosomes, remain a pre-clinical technology despite their great clinical potential. A first-in-human clinical trial of MSC treatment for BPD was performed as a phase I dose-escalation trial using umbilical cord blood-derived MSC. That trial demonstrated the short- and long-term safety and feasibility of MSC, given that significantly reduced inflammatory marker expression was observed in tracheal aspirates. As of recently, several clinical trials of MSC use for BPD are ongoing or are planned in some countries to investigate the efficacy of MSC in the prevention or treatment of BPD in premature infants. Many clinicians are currently awaiting the results from these trials so that MSC can be used clinically for human BPD.
支气管肺发育不良(BPD)是一种发生于接受过补充氧气和机械通气治疗的早产儿的慢性肺部疾病。尽管围产期和新生儿医学取得了重大进展,但在降低BPD发病率方面进展有限。间充质干细胞(MSC)的应用是一种针对多种疾病的有前景且创新的治疗方法,因为它们易于提取,具有低免疫原性、抗炎特性和再生能力。根据多项使用BPD动物模型的临床前研究,MSC在BPD中的一种作用机制主要归因于MSC衍生的体液因子的旁分泌作用,如白细胞介素(IL)-6、IL-8、血管内皮生长因子、胶原蛋白和弹性蛋白,而非MSC的多向分化和再生能力。源自MSC的无细胞制剂,包括条件培养基和外泌体,尽管具有巨大的临床潜力,但仍处于临床前技术阶段。一项针对BPD的MSC治疗的首次人体临床试验作为I期剂量递增试验,使用了脐带血来源的MSC进行。该试验证明了MSC的短期和长期安全性及可行性,因为在气管吸出物中观察到炎症标志物表达显著降低。截至最近,一些国家正在进行或计划进行多项关于MSC用于BPD的临床试验,以研究MSC在预防或治疗早产儿BPD方面的疗效。许多临床医生目前正在等待这些试验的结果,以便MSC能够临床用于人类BPD的治疗。