Niu Xinhui, Zhang Lina, Xing Shaoliang, Liu Jinrui, Li Deming, Wang Yating, Wang Yi, Su Manman
Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
NMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, Changchun 130024, China.
Int J Mol Sci. 2025 Mar 5;26(5):2314. doi: 10.3390/ijms26052314.
Acute lung injury (ALI) is a life-threatening condition triggered by pneumonia, viral infections, or physical trauma. It manifests clinically as progressive respiratory failure and refractory hypoxemia. Using a lipopolysaccharide (LPS)-induced acute lung injury mouse model, we demonstrated that amniotic mesenchymal stem cells (AMSCs) exhibit robust reparative and anti-inflammatory properties. Our analysis encompassed inflammatory mediators; histological damage; tight junction integrity; epithelial-mesenchymal transition (EMT); and the TGF-β/Smad, TLR4/NF-κB/MAPK, pyroptosis, and apoptosis signaling pathways. Our key results demonstrated that in ALI-afflicted mice, AMSCs exhibited targeted pulmonary tropism, homing in on injured alveolar regions, where they restored the morphology and functionality of damaged tissues and organelles, re-established lung barrier function, and attenuated the aberrantly activated TLR4/NF-κB/MAPK and TGF-β/Smad pathways associated with inflammation. These coordinated mechanisms contributed to pyroptosis, apoptosis, and fibrosis suppression. In conclusion, AMSCs mitigated the inflammatory injury process in ALI mice through multiple mechanisms, thereby supporting the potential development of MSC-based therapeutic strategies.
急性肺损伤（ALI）是一种由肺炎、病毒感染或身体创伤引发的危及生命的病症。其临床症状表现为进行性呼吸衰竭和难治性低氧血症。利用脂多糖（LPS）诱导的急性肺损伤小鼠模型，我们证明了羊膜间充质干细胞（AMSCs）具有强大的修复和抗炎特性。我们的分析涵盖了炎症介质、组织学损伤、紧密连接完整性、上皮-间质转化（EMT）以及TGF-β/Smad、TLR4/NF-κB/MAPK、细胞焦亡和凋亡信号通路。我们的关键结果表明，在患有ALI的小鼠中，AMSCs表现出靶向肺嗜性，归巢至受损的肺泡区域，在那里它们恢复了受损组织和细胞器的形态及功能，重新建立了肺屏障功能，并减弱了与炎症相关的异常激活的TLR4/NF-κB/MAPK和TGF-β/Smad通路。这些协同机制有助于抑制细胞焦亡、凋亡和纤维化。总之，AMSCs通过多种机制减轻了ALI小鼠的炎症损伤过程，从而支持了基于间充质干细胞的治疗策略的潜在发展。
