Department of Otolaryngology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Plastic and Reconstructive Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Allergol Immunopathol (Madr). 2022 Jul 1;50(4):105-114. doi: 10.15586/aei.v50i4.572. eCollection 2022.
Allergic rhinitis (AR) is a common immune disease of the nasal mucosa characterized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchymal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti- inflammatory potential in treating AR.
The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model.
The AR murine model was induced by repeated sensitization and challenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated.
Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symptoms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 () at messenger RNA and protein levels in the nasal mucosa.
BMSC-CM could ameliorate allergic inflammation and regulate the balance of Th cells, and the underlying mechanism was closely related to signaling pathway. The immunoregulatory effects of BMSCs could be achieved through paracrine function, and nasal dripping of BMSC-CM might be a novel approach for the treatment of AR.
变应性鼻炎（AR）是一种常见的鼻黏膜免疫性疾病，其特征是在易感人群中暴露于过敏原后，免疫球蛋白 E（IgE）介导的过敏炎症。先前的报告表明，骨髓间充质干细胞（BMSCs）可以减轻过敏炎症。然而，关于 BMSCs 的培养上清液（条件培养基，CM）是否具有类似的抗炎潜力来治疗 AR，目前知之甚少。
本研究旨在评估源自 BMSCs 的条件培养基（BMSC-CM）对 AR 小鼠模型中过敏炎症的免疫调节作用。
通过反复用卵清蛋白（OVA）致敏和激发来诱导 AR 小鼠模型。随后评估 AR 小鼠的过敏症状、细胞因子水平、鼻黏膜组织病理学特征以及辅助性 T 细胞 1（Th1）：辅助性 T 细胞 2（Th2）细胞比值。
BMSC-CM 治疗与 BMSCs 治疗一样，可有效减轻过敏症状并抑制鼻黏膜嗜酸性粒细胞浸润。与用未培养的新鲜培养基处理的 AR 小鼠相比，BMSC-CM 或 BMSCs 处理后，血清中 OVA 特异性 IgE 和白细胞介素 4 水平降低，干扰素 γ水平升高。流式细胞术分析显示，OVA 致敏后 Th1：Th2 细胞比值降低，BMSC-CM 和 BMSCs 处理可逆转该比值。此外，数据显示 BMSC-CM 可抑制鼻黏膜中信号转导和转录激活因子 6（STAT6）信使 RNA 和蛋白水平的产生。
BMSC-CM 可改善过敏炎症并调节 Th 细胞平衡，其潜在机制与 STAT6 信号通路密切相关。BMSCs 的免疫调节作用可以通过旁分泌功能实现，鼻滴注 BMSC-CM 可能是治疗 AR 的一种新方法。
