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已发表论文
脐带间充质干细胞来源的细胞外纳米囊泡通过 hsa-miR-27b-3p 介导抑制 PI3K/AKT/STAT3 信号通路调节 Th17/Treg 平衡从而缓解结肠炎
Authors Zhou Y, Wang Y, Huang Y, Li P , Zeng Y, Fan W, Lin Z, Ye X, Chen J, Jin K , Mou X, Chen X
Received 26 September 2025
Accepted for publication 10 December 2025
Published 25 December 2025 Volume 2025:20 Pages 15683—15704
DOI https://doi.org/10.2147/IJN.S565416
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yan Shen
Yuanhao Zhou,1– 3,* Yuanyuan Wang,1– 3,* Yilin Huang,1,2 Ping Li,1,2 Yan Zeng,1,2 Weijiao Fan,1,2 Zhiwei Lin,4 Xiangming Ye,1 Jinyang Chen,4 Ketao Jin,5 Xiaozhou Mou,1,2 Xiaoyi Chen1,2
1Center for Rehabilitation Medicine, Rehabilitation and Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Zhejiang Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine, Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, People’s Republic of China; 4HealthRegen (Hangzhou) Biotechnology Co., Ltd., Hangzhou, Zhejiang, 310000, People’s Republic of China; 5Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310003, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaozhou Mou, Email mouxz@zju.edu.cn Xiaoyi Chen, Email chenxiaoyi@hmc.edu.cn
Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, characterized by persistent immune dysregulation. Umbilical cord mesenchymal stem cell-derived extracellular nanovesicles (MSC NVs) exhibit immunomodulatory properties, demonstrating significant therapeutic potential for clinical applications. This study sought to investigate the therapeutic effects of MSC NVs against colitis and elucidate the underlying mechanisms.
Methods: MSC NVs were prepared from umbilical cord MSCs using a continuous filtration-extrusion method. The therapeutic effects of MSC NVs were assessed by tail vein injection in a murine model of DSS-induced colitis.
Results: MSC NVs significantly markedly ameliorated colitis-associated symptoms, including body weight loss, colon length reduction, and elevated disease activity index scores. MSC NVs not only mitigated colitis-induced intestinal barrier impairment and inflammatory responses, but also exhibited targeted biodistribution to inflamed colonic lesions. Unexpectedly, administration of MSC-NVs via the tail vein significantly altered the gut microbial composition in colitic mice, particularly enhancing the relative abundances of beneficial commensal genera Lachnoclostridium and Dubosiella, consequently reestablishing microbial homeostasis. Moreover, MSC NVs modulated the T help (Th) 17/ regulatory T (Treg) balance within the colonic lamina propria through delivery of hsa-miR-27b-3p, which directly targeted the PIK3CA gene, thereby inhibiting PI3K/AKT/STAT3 signaling pathway activation and exerting anti-colitis effects.
Conclusion: This study demonstrated that MSC NVs significantly alleviated DSS-induced colitis by modulating Th17/Treg balance in the colonic lamina propria, with hsa-miR-27b-3p identified as the key mediator through PIK3CA targeting and PI3K/AKT/STAT3 pathway inhibition. These findings highlight the therapeutic potential of filtration–extrusion-prepared MSC NVs as a safe and effective nanomedicine for IBD treatment.
Keywords: colitis, umbilical cord mesenchymal stem cells, extracellular nanovesicles, Th17/Treg balance, microRNAs, PI3K/AKT/STAT3 pathway
1Center for Rehabilitation Medicine, Rehabilitation and Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Zhejiang Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine, Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, People’s Republic of China; 4HealthRegen (Hangzhou) Biotechnology Co., Ltd., Hangzhou, Zhejiang, 310000, People’s Republic of China; 5Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310003, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaozhou Mou, Email mouxz@zju.edu.cn Xiaoyi Chen, Email chenxiaoyi@hmc.edu.cn
Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, characterized by persistent immune dysregulation. Umbilical cord mesenchymal stem cell-derived extracellular nanovesicles (MSC NVs) exhibit immunomodulatory properties, demonstrating significant therapeutic potential for clinical applications. This study sought to investigate the therapeutic effects of MSC NVs against colitis and elucidate the underlying mechanisms.
Methods: MSC NVs were prepared from umbilical cord MSCs using a continuous filtration-extrusion method. The therapeutic effects of MSC NVs were assessed by tail vein injection in a murine model of DSS-induced colitis.
Results: MSC NVs significantly markedly ameliorated colitis-associated symptoms, including body weight loss, colon length reduction, and elevated disease activity index scores. MSC NVs not only mitigated colitis-induced intestinal barrier impairment and inflammatory responses, but also exhibited targeted biodistribution to inflamed colonic lesions. Unexpectedly, administration of MSC-NVs via the tail vein significantly altered the gut microbial composition in colitic mice, particularly enhancing the relative abundances of beneficial commensal genera Lachnoclostridium and Dubosiella, consequently reestablishing microbial homeostasis. Moreover, MSC NVs modulated the T help (Th) 17/ regulatory T (Treg) balance within the colonic lamina propria through delivery of hsa-miR-27b-3p, which directly targeted the PIK3CA gene, thereby inhibiting PI3K/AKT/STAT3 signaling pathway activation and exerting anti-colitis effects.
Conclusion: This study demonstrated that MSC NVs significantly alleviated DSS-induced colitis by modulating Th17/Treg balance in the colonic lamina propria, with hsa-miR-27b-3p identified as the key mediator through PIK3CA targeting and PI3K/AKT/STAT3 pathway inhibition. These findings highlight the therapeutic potential of filtration–extrusion-prepared MSC NVs as a safe and effective nanomedicine for IBD treatment.
Keywords: colitis, umbilical cord mesenchymal stem cells, extracellular nanovesicles, Th17/Treg balance, microRNAs, PI3K/AKT/STAT3 pathway