Chen Jing, Liu Shuang, Zou Jizhen, Wang Yi, Ge Haiyan, Hui Yi, Huang Siyuan, Li Wei, Na Weilan, Huang Xiaolan, Bai Lin, Huang Yiying, Qu Dong
Department of Critical Medicine, Children's Hospital Affiliated Capital Institute of Pediatrics, Beijing, China.
Department of Critical Care Medicine, Capital Institute of Pediatrics, Beijing, China.
Front Pediatr. 2025 May 29;13:1560915. doi: 10.3389/fped.2025.1560915. eCollection 2025.
To investigate the therapeutic efficacy of human umbilical cord blood mesenchymal stem cell-derived exosomes (hUCMSC-Exo) in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model and compare the effects of different administration routes.
An ALI mouse model was established through intratracheal LPS injection. Mice received hUCMSC-Exo through tail vein injection, nasal drip, or atomization at 4-and-24 h post-modeling, with comparisons made across low, medium, and high doses. Mice were categorized into three groups: control, LPS model, and experimental ( = 8). Histopathological scoring assessed lung inflammation after 48 h; and inflammatory cytokine levels (TNF-α, IL-6, IL-1β, and IL-10) in serum and bronchoalveolar lavage fluid (BALF) were quantified by enzyme-linked immunosorbent assay (ELISA).
In a murine model of LPS-induced ALI, administration of hUCMSC-Exo via intravenous, intranasal, or nebulized routes at 4 and 24 h post-LPS exposure significantly attenuated pulmonary inflammation, as evidenced by reduced alveolar inflammatory cell infiltration, hemorrhage, and edema in histopathological analysis (except the nebulized low-dose group). ELISA revealed that hUCMSC-Exo markedly decreased serum and bronchoalveolar lavage fluid (BALF) levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β ( < 0.05) while increasing IL-10 levels. Dose-dependent effects were observed across routes: intravenous high-dose (Exo-VH) outperformed medium- and low-dose groups ( < 0.05); intranasal medium-dose (Exo-NM) was superior to low-dose (Exo-NL; < 0.05), with no significant difference between medium and high doses ( > 0.05); nebulized high-dose (Exo-AH) demonstrated enhanced efficacy over medium- (Exo-AM; < 0.05) and low-dose (Exo-AL; < 0.05). At an equivalent dose (5 × 10⁸ particles), intravenous delivery achieved superior lung injury score reduction and cytokine modulation compared to intranasal and nebulized routes ( < 0.05), whereas the latter two showed comparable efficacy ( > 0.05). These findings collectively highlight the therapeutic potential of hUCMSC-Exo in ALI, with intravenous administration emerging as the optimal route at the tested dose.
hUCMSC-Exo effectively attenuates LPS-induced ALI in mice. At the tested dose (5 × 10⁸ particles), intravenous delivery exhibited superior therapeutic efficacy over intranasal and nebulized routes.
研究人脐带血间充质干细胞来源的外泌体（hUCMSC-Exo）在脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠模型中的治疗效果，并比较不同给药途径的作用。
通过气管内注射LPS建立ALI小鼠模型。在建模后4小时和24小时，小鼠通过尾静脉注射、滴鼻或雾化方式接受hUCMSC-Exo，并设置低、中、高剂量进行比较。将小鼠分为三组：对照组、LPS模型组和实验组（每组 = 8只）。48小时后通过组织病理学评分评估肺部炎症；采用酶联免疫吸附测定（ELISA）法对血清和支气管肺泡灌洗液（BALF）中的炎性细胞因子水平（TNF-α、IL-6、IL-1β和IL-10）进行定量分析。
在LPS诱导的ALI小鼠模型中，在LPS暴露后4小时和24小时通过静脉、鼻内或雾化途径给予hUCMSC-Exo可显著减轻肺部炎症，组织病理学分析显示肺泡炎性细胞浸润、出血和水肿减少（雾化低剂量组除外）。ELISA结果显示，hUCMSC-Exo可显著降低血清和支气管肺泡灌洗液（BALF）中促炎细胞因子TNF-α、IL-6和IL-1β的水平（P < 0.05），同时提高IL-10水平。各给药途径均观察到剂量依赖性效应：静脉高剂量组（Exo-VH）优于中、低剂量组（P < 0.05）；鼻内中剂量组（Exo-NM）优于低剂量组（Exo-NL；P < 0.05），中、高剂量组之间无显著差异（P > 0.05）；雾化高剂量组（Exo-AH）的疗效优于中剂量组（Exo-AM；P < 0.05）和低剂量组（Exo-AL；P < 0.05）。在等效剂量（5×10⁸个颗粒）下，与鼻内和雾化途径相比，静脉给药在降低肺损伤评分和调节细胞因子方面效果更佳（P < 0.05），而后两者疗效相当（P > 0.05）。这些结果共同表明hUCMSC-Exo在ALI中具有治疗潜力，在所测试剂量下静脉给药是最佳途径。
hUCMSC-Exo可有效减轻LPS诱导的小鼠ALI。在所测试剂量（5×10⁸个颗粒）下，静脉给药的治疗效果优于鼻内和雾化途径。
