Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Duanxing West Road, Jinan, Shandong, 250033, China.
Department of Otorhinolaryngology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, No. 3002 Sungang West Road, Shenzhen, Guangdong Province, 518000, China.
Inflamm Res. 2024 Oct;73(10):1819-1832. doi: 10.1007/s00011-024-01933-1. Epub 2024 Aug 24.
To investigate the immunomodulatory effects and potential mechanisms of human nasal mucosa-derived mesenchymal stem cells(hNMSCs) on mouse allergic rhinitis, and to compare them with human umbilical cord-derived mesenchymal stem cells (hUCMSCs).
hNMSCs and hUCMSCs were isolated and cultured for identification from human nasal mucosa and umbilical cord tissues. A co-culture system of LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs was employed.Changes in inflammatory factors in RAW264.7 cells and the culture medium as well as the expression of NF-κB signaling pathway in RAW264.7 cells were detected. Forty-eight BALB/c mice were randomly divided into control, OVA, hNMSCs, and hUCMSCs groups. An allergic rhinitis (AR) model was established through ovalbumin (OVA) stimulation and treated with hNMSCs and hUCMSCs. Subsequent assessments included related symptoms, biological changes, and the expression of the NF-κB signaling pathway in the nasal mucosa of mice.
MSCs can be successfully isolated from human nasal mucosa. Both hNMSCs and hUCMSCs interventions significantly reverseed the inflammation induced by LPS and suppressed the upregulation of the NF-κB signaling pathway in RAW264.7 cells. Treatment with hNMSCs and hUCMSCs alleviated mouse allergic symptoms, reduced levels of total IgE, OVA-specific IgE and IgG1 in mouse serum, TH2-type cytokines and chemokines in mouse nasal mucosa, and TH2-type cytokines in mouse spleen culture medium, while also inhibiting the expression of the NF-κB signaling pathway in the nasal mucosa of mice. moreover, the hNMSCs group showed a more significant reduction in OVA-specific IgG1 in serum and IL-4 expression levels in mouse spleen culture medium compared to the hUCMSCs group.
Our findings suggest that hNMSCs can ameliorate allergic rhinitis in mice, with a certain advantage in anti-inflammatory effects compared to hUCMSCs. The NF-κB pathway is likely involved in the anti-inflammatory regulation process by hNMSCs.Therefore, hNMSCs might represent a novel therapeutic approach for allergic rhinitis.
研究人鼻腔黏膜间充质干细胞(hNMSCs)对过敏性鼻炎的免疫调节作用及其机制,并与脐带来源间充质干细胞(hUCMSCs)进行比较。
从人鼻腔黏膜和脐带组织中分离培养 hNMSCs 和 hUCMSCs 进行鉴定。采用脂多糖(LPS)刺激 RAW264.7 细胞/小鼠腹腔巨噬细胞与 MSC 的共培养体系,检测 RAW264.7 细胞及其培养基中炎症因子的变化,以及 RAW264.7 细胞中 NF-κB 信号通路的表达。将 48 只 BALB/c 小鼠随机分为对照组、OVA 组、hNMSCs 组和 hUCMSCs 组。通过卵清蛋白(OVA)刺激建立过敏性鼻炎(AR)模型,并用 hNMSCs 和 hUCMSCs 进行治疗。随后评估包括相关症状、生物学变化以及小鼠鼻黏膜 NF-κB 信号通路的表达。
成功从人鼻腔黏膜中分离出 MSC。hNMSCs 和 hUCMSCs 干预均能显著逆转 LPS 诱导的炎症,并抑制 RAW264.7 细胞中 NF-κB 信号通路的上调。hNMSCs 和 hUCMSCs 治疗可减轻小鼠过敏性症状,降低小鼠血清总 IgE、OVA 特异性 IgE 和 IgG1 水平,降低小鼠鼻黏膜 TH2 型细胞因子和趋化因子水平,降低小鼠脾培养液 TH2 型细胞因子水平,抑制小鼠鼻黏膜 NF-κB 信号通路的表达。此外,与 hUCMSCs 组相比,hNMSCs 组小鼠血清中 OVA 特异性 IgG1 及脾培养液中 IL-4 表达水平降低更为显著。
hNMSCs 可改善过敏性鼻炎小鼠的症状,在抗炎作用方面优于 hUCMSCs。NF-κB 通路可能参与了 hNMSCs 的抗炎调节过程。因此,hNMSCs 可能成为治疗过敏性鼻炎的一种新方法。