Zhao Yuan, Ding Yabing, Wang Zhaoyan, Wang Qian, Ye Dou, Luan Zuo
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Department of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing, China.
Cell Transplant. 2025 Jan-Dec;34:9636897251326899. doi: 10.1177/09636897251326899. Epub 2025 Mar 27.
This study aimed to investigate the impact of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) on food allergy (FA) mice induced by ovalbumin. The percentage of regulatory T cells (Tregs) was assessed by administering hUC-MSCs intravenously to FA mouse models with oral challenges, allergic responses and levels of related allergic cytokines. The phenotypes of hUC-MSCs were analysed using flow cytometric analysis. Immunohistochemistry was used for histology observation. Real-time polymerase chain reaction (PCR) was used for gene expression. Jejunum tissue was analysed by transcriptome sequencing. Our results demonstrated that in the current FA model, hUC-MSC therapy significantly alleviated allergic responses and diarrhoea. Levels of immunoglobulin E (IgE), as well as cytokines, such as interleukin (IL)-6 and tumour necrosis factor-α associated with T helper 2 cells, were reduced. Conversely, transforming growth factor (TGF)-β levels increased with hUC-MSC therapy. In addition, enhanced TGF-β expression along with IL-10 messenger ribonucleic acid levels and an increased percentage of CD4Foxp3 Tregs were observed. In long-term FA mice models, hUC-MSC therapy exhibited sustained effects in mitigating rectal temperature decrease and mortality rates while reducing the levels of IgE, IL-6 and proportion of IgE+ cells; it also elevated TGF-β levels. Furthermore, hUC-MSC therapy attenuated pathological injury in both current and long-term FA mouse models. Transcriptome sequencing showed that upregulated differentially expressed genes were mainly concentrated in neural activation-ligand interaction, the cyclic guanosine monophosphate-protein kinase G signalling pathway and the TGF-β signalling pathway. The hUC-MSC therapy holds promise for alleviating both immediate and persistent FA conditions; targeting TGF-β and IL-10 secreted by hUC-MSCs may be a potential approach for treating FA.
本研究旨在探讨人脐带间充质基质细胞（hUC-MSCs）对卵清蛋白诱导的食物过敏（FA）小鼠的影响。通过对有口服激发、过敏反应及相关过敏细胞因子水平的FA小鼠模型静脉注射hUC-MSCs，评估调节性T细胞（Tregs）的百分比。采用流式细胞术分析hUC-MSCs的表型。免疫组织化学用于组织学观察。实时聚合酶链反应（PCR）用于基因表达分析。通过转录组测序分析空肠组织。我们的结果表明，在当前的FA模型中，hUC-MSC治疗显著减轻了过敏反应和腹泻。免疫球蛋白E（IgE）水平以及与辅助性T细胞2相关的细胞因子，如白细胞介素（IL）-6和肿瘤坏死因子-α水平降低。相反，hUC-MSC治疗使转化生长因子（TGF）-β水平升高。此外，观察到TGF-β表达增强，同时白细胞介素-10信使核糖核酸水平升高，CD4Foxp3 Tregs百分比增加。在长期FA小鼠模型中，hUC-MSC治疗在减轻直肠温度降低和死亡率方面表现出持续效果，同时降低了IgE、IL-6水平以及IgE+细胞比例；它还提高了TGF-β水平。此外，hUC-MSC治疗减轻了当前和长期FA小鼠模型中的病理损伤。转录组测序表明，上调的差异表达基因主要集中在神经激活-配体相互作用、环磷酸鸟苷-蛋白激酶G信号通路和TGF-β信号通路。hUC-MSC治疗有望缓解即刻和持续性FA病症；靶向hUC-MSCs分泌的TGF-β和IL-10可能是治疗FA的一种潜在方法。
