Chronic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Previous studies have shown that mesenchymal stromal/stem cells (MSCs) exert anti-inflammatory effects on asthma via regulation of the immune cells. However, the therapeutic mechanism of MSCs, especially the mechanism of airway remodeling in chronic asthma, remains to be elucidated. Here, we aimed to investigate the therapeutic effect of MSCs on airway remodeling in chronic asthma and explored the mechanisms by analyzing the polarization phenotype of macrophages in the lungs. We established a mouse model of chronic asthma induced by ovalbumin (OVA) and evaluated the effect of MSCs on airway remodeling. The data showed that MSCs treatment before the challenge exerted protective effects on OVA-induced chronic asthma, i.e., decreased the inflammatory cell infiltration, Th2 cytokine levels, subepithelial extracellular matrix deposition, and transforming growth factor β (TGF-β)/Smad signaling. Additionally, we found that MSCs treatment markedly suppressed macrophage M2 polarization in lung tissue. At the same time, MSCs treatment inhibited NF-κB p65 nuclear translocation, ER stress, and oxidative stress in the OVA-induced chronic allergic airway remodeling mice model. In conclusion, these results demonstrated that MSCs treatment prevents OVA-induced chronic airway remodeling by suppressing macrophage M2 polarization, which may be associated with the dual inhibition of ER stress and oxidative stress. This discovery may provide a new theoretical basis for the future clinical application of MSCs.

慢性哮喘的特征是气道高反应性、炎症和重塑。先前的研究表明，间充质基质/干细胞（MSC）通过调节免疫细胞对哮喘发挥抗炎作用。然而，间充质干细胞的治疗机制，特别是慢性哮喘气道重塑的机制仍有待阐明。在此，我们旨在研究间充质干细胞对慢性哮喘气道重塑的治疗作用，并通过分析肺部巨噬细胞的极化表型探讨其机制。我们建立了卵清蛋白（OVA）诱导的慢性哮喘小鼠模型，并评估了 MSC 对气道重塑的作用。数据显示，攻击前的MSC治疗对OVA诱导的慢性哮喘具有保护作用，即减少炎症细胞浸润、Th2细胞因子水平、上皮下细胞外基质沉积和转化生长因子β(TGF-β)/Smad信号传导。此外，我们发现 MSC 治疗显着抑制了肺组织中巨噬细胞 M2 极化。同时，MSCs 治疗可抑制 OVA 诱导的慢性过敏性气道重塑小鼠模型中的 NF-κB p65 核转位、ER 应激和氧化应激。总之，这些结果表明 MSC 治疗通过抑制巨噬细胞 M2 极化来预防 OVA 诱导的慢性气道重塑，这可能与 ER 应激和氧化应激的双重抑制有关。这一发现可能为MSCs未来的临床应用提供新的理论基础。