Background: Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD. Objectives: To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate the role of autophagy in this process. Method: ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) from postnatal day 0 (P0) to P7, and returned to room air until P14 to mimic BPD. ADSC-Exos was treated by intratracheal or intravenous administration on P4. Treated animals and appropriate controls were harvested on P7 and P14 for assessment of pulmonary parameters. Results: Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration. Conclusion: The intratracheal administration of ADSC-Exos significantly improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part.

中文翻译：

---

脂肪干细胞衍生的外泌体减轻新生大鼠支气管肺发育不良并调节自噬

背景：间充质干细胞衍生的外泌体（MSC-Exos）疗法在与新生儿医学相关的病理学模型（例如支气管肺发育不良（BPD））的临床前模型中显示出前景。脂肪干细胞（ADSC）已被认为是最有前途的干细胞来源之一。自噬在调节细胞内条件、维持细胞生长发育、参与BPD发病机制中发挥着关键作用。目的：探讨 ADSC-Exos 对 BPD 的潜在治疗作用，并阐明自噬在此过程中的作用。方法：通过超速离心从 ADSC 条件培养基中分离 ADSC-Exos，并通过透射电子显微镜 (TEM)、纳米粒子追踪分析 (NTA) 和蛋白质印迹 (WB) 进行表征。新生大鼠从出生后第 0 天 (P0) 到 P7 暴露于高氧 (90% O2) 中，并返回室内空气直到 P14 以模拟 BPD。ADSC-Exos 在 P4 时通过气管内或静脉内给药进行治疗。在 P7 和 P14 时收获经处理的动物和适当的对照以评估肺部参数。结果：高氧暴露的大鼠表现出明显的肺泡简化，径向肺泡计数（RAC）减少和平均线性截距（MLI）增加，血管发育受损，血管内皮生长因子（VEGF）和CD31表达低，并刺激炎症增加TNF-α、IL-1β 和 IL-6 表达降低，IL-10 表达降低。同时，高氧暴露的大鼠会阻断自噬流，Beclin1、LC3B、LC3BII/I 比值水平较低，p62 水平较高。ADSC-Exos 给药可以保护新生儿肺组织免受高氧诱导的肺泡和血管发育停滞的影响，减少炎症并促进自噬。气管内给药比静脉内给药更有效。结论：气管内给予 ADSC-Exos 显着改善高氧诱导的 BPD 中的肺泡化和肺血管化停滞，这在一定程度上与促进自噬有关。