间充质干细胞来源的胞外囊泡治疗新生儿支气管肺发育不良的研究进展

Progress of Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Treatment of Neonatal Bronchopulmonary Dysplasia

支气管肺发育不良(bronchopulmonary dysplasia,BPD)是早产儿的慢性肺部疾病,尤其是极早产儿(出生胎龄小于32周)最常见的并发症。尽管围产期救治及护理取得了进步,但现代临床管理仍然缺乏专门促进肺修复和肺生长的疗法。间充质干细胞(mesenchymal stem cells,MSCs)是一类具有多向分化潜能的干细胞,其最新进展揭示了干细胞/祖细胞修复受损器官的前景。但MSCs本身存在的临床风险导致其无法实现更加广泛的应用。研究表明,在BPD动物模型中,MSCs来源的细胞外囊泡(MSCs-derived extracellular vesicles,MSC-EVs)可以通过下调纤维化因子、减轻炎症反应、促进血管生成、抗细胞凋亡、抗氧化应激等途径促进肺血管生成和肺泡的发育,减少肺动脉高压和炎症,在BPD肺损伤修复中发挥重要作用。本文主要综述了MSC-EVs治疗早产儿BPD的有潜力的临床前证据及可能机制,为今后其在BPD的临床应用提供新的治疗思路。

Bronchopulmonary dysplasia(BPD)is a chronic lung disease of preterm infants,particularly being the most common complication among extremely preterm infants(those born with a gestational age of less than 32 weeks).Despite advances in perinatal treatment and care,modern clinical management still lacks therapies specifically designed to promote lung repair and growth.Mesenchymal stem cells(MSCs)are a type of stem cells with multi-differentiation potential,and recent advances have revealed their potential to repair damaged organs through stem/progenitor cell-mediated regeneration.However,clinical risks associated with MSCs have hindered their broader applications.Research indicates that in BPD animal models,MSC-derived extracellular vesicles(MSC-EVs)manage to promote pulmonary angiogenesis,facilitate alveolar development,reduce pulmonary arterial hypertension,and alleviate pulmonary inflammation by downregulating fibrotic factors,alleviating inflammatory responses,and promoting angiogenesis,anti-apoptosis,and resistance to oxidative stress.Therefore,they play critical roles in the repair of lung injuries associated with BPD.This article reviews the potential preclinical evidence and possible mechanisms of MSC-EV-associated therapy in the treatment of neonatal BPD,providing new therapeutic insights for its future clinical application in neonatal BPD.