PDF(Pubmed)
Abstract：
This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.
摘要：
这项研究比较了源自过表达hsa-let-7i-5p的RAW264.7细胞的工程化外泌体（工程化外泌体）与来自人胎盘来源的间充质干细胞（hpMSC外泌体）的外泌体对脓毒症诱导的急性肺损伤的治疗效果。成年雄性C57BL/6小鼠分为脂多糖（LPS），LPS加工程外泌体（LEExo），或LPS加hpMSC外泌体（LMExo）组，与对照组并驾齐驱。结果显示,肺损伤评分(基于病理组织学特征)和肺功能改变的水平,组织水肿，LEExo和LMExo组的白细胞浸润具有可比性，并明显低于LPS组（均p<0.05）。此外，炎症水平（核因子-κB激活，细胞因子上调)，巨噬细胞活化(缺氧诱导因子-1α活化，M1相位极化)，氧化，与LPS组相比，LEExo和LMExo组的细胞凋亡减少（均p<0.05）。hsa-let-7i-5p的抑制减弱了工程和hpMSC外泌体的治疗效果。这些发现强调了富含hsa-let-7i-5p的工程外泌体的有效治疗能力，以及它们作为hpMSC外泌体替代脓毒症治疗的潜力。对工程化外泌体的作用机制和优化的持续研究可以为其未来的临床应用铺平道路。
