Wu Jiajun, Yang Zhen, Wang Daoyuan, Xiao Yihui, Shao Jia, Ren Kaiqun
The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University, Changsha, 410013, China.
The Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province, Medical College, Hunan Normal University, Changsha, 410013, China.
Curr Stem Cell Res Ther. 2025;20(3):302-316. doi: 10.2174/011574888X314032240429113240.
The aim of this study was to investigate the role of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) in regulating the intestinal type 2 immune response for either protection or therapy.
hUCMSC-Exo was considered a novel cell-free therapeutic product that shows promise in the treatment of various diseases. Type 2 immunity is a protective immune response classified as T-helper type 2 (Th2) cells and is associated with helminthic infections and allergic diseases. The effect of hUCMSC-Exo on intestinal type 2 immune response is not clear.
C57BL/6 mice were used to establish intestinal type 2 immune response by administering of and treated with hUCMSC-Exo before or after infection. Intestinal organoids were isolated and co-cultured with IL-4 and hUCMSC-Exo. Then, we monitored the influence of hUCMSC-Exo on type 2 immune response by checking adult worms, the hyperplasia of tuft and goblet cells Result: hUCMSC-Exo significantly delays the colonization of in subserosal layer of duodenum on day 7 post-infection and promotes the hyperplasia of tuft cells and goblet cells on day 14 post-infection. HUCMSC-Exo enhances the expansion of tuft cells in IL-4 treated intestinal organoids, and promotes lytic cell death.
Our study demonstrates hUCMSC-Exo may benefit the host by increasing the tolerance at an early infection stage and then enhancing the intestinal type 2 immune response to impede the helminth during Th2 priming. Our results show hUCMSC-Exo may be a positive regulator of type 2 immune response, suggesting hUCMSC-Exo has a potential therapeutic effect on allergic diseases.
本研究旨在探讨人脐带间充质干细胞来源的外泌体（hUCMSC-Exo）在调节肠道2型免疫反应以进行保护或治疗方面的作用。
hUCMSC-Exo被认为是一种新型的无细胞治疗产品，在治疗各种疾病方面显示出前景。2型免疫是一种被归类为辅助性T细胞2型（Th2）细胞的保护性免疫反应，与蠕虫感染和过敏性疾病有关。hUCMSC-Exo对肠道2型免疫反应的影响尚不清楚。
使用C57BL/6小鼠通过给予 建立肠道2型免疫反应，并在感染 之前或之后用hUCMSC-Exo进行治疗。分离肠道类器官并与白细胞介素-4和hUCMSC-Exo共培养。然后，我们通过检查成虫、簇状细胞和杯状细胞的增生来监测hUCMSC-Exo对2型免疫反应的影响。结果：hUCMSC-Exo在感染后第7天显著延迟了 在十二指肠浆膜下层的定植，并在感染后第14天促进了簇状细胞和杯状细胞的增生。HUCMSC-Exo增强了白细胞介素-4处理的肠道类器官中簇状细胞的扩增，并促进了溶细胞死亡。
我们的研究表明，hUCMSC-Exo可能通过在感染早期增加耐受性，然后增强肠道2型免疫反应以在Th2启动期间阻碍蠕虫，从而使宿主受益。我们的结果表明hUCMSC-Exo可能是2型免疫反应的正调节剂，提示hUCMSC-Exo对过敏性疾病具有潜在治疗作用。
