Li Hongkun, Zhang Yuyue, Du Simin, Shen Jinghan, Liu Xingyan, Jing Jie
School and Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou, China.
Front Immunol. 2025 May 13;16:1543702. doi: 10.3389/fimmu.2025.1543702. eCollection 2025.
The global prevalence of inflammatory bowel disease (IBD) has significantly increased in recent decades. IBD is a long-term, recurring, gastrointestinal inflammatory condition that mainly comprises two primary clinical types: ulcerative colitis and Crohn's disease. The current treatment paradigm for IBD primarily focuses on symptom management. However, this approach does not support mucosal epithelial repair, maintenance of barrier homeostasis, or regulation of biological functions in the gut. Conventional therapies rely on the frequent use of high-dose medications, including antibiotics, nonsteroidal anti-inflammatory drugs, biological agents, and immunomodulators. Recently, mesenchymal stem/stromal cells (MSCs) have gained interest in tissue regeneration owing to their unique ability to differentiate and secrete regulatory factors, including extracellular vesicles (EVs), which play crucial roles in abnormal organization. Various routes of administration have been explored in preclinical and clinical studies to deliver MSCs from diverse tissue sources. The routes include intraperitoneal, intravenous, and local (intracolonic or rectal) delivery. The MSCs employed were obtained from various tissues, including bone marrow, umbilical cord, and adipose tissue. This article reviews the research framework for the application of MSCs and EVs secretion in the treatment of IBD, emphasizing key immunological effects, such as immune microenvironment regulation, intestinal barrier stabilization, and therapeutic approaches targeting intestinal barrier disorders. The discussion primarily focuses on the advantages of MSCs over other biologics, impairment of gut mucosal tissue-resident mesenchymal stem cells in IBD development, immune targets (at the cellular and molecular levels) within the framework of IBD, and the reparative effects of MSCs in the microenvironment of IBD. We aimed to present an overview of the current trends in MSC research and therapy, as well as to identify the challenges and future directions that must be addressed to advance research on MSC-mediated therapeutic strategies for IBD.
近几十年来，炎症性肠病（IBD）的全球患病率显著上升。IBD是一种长期反复发生的胃肠道炎症性疾病，主要包括两种主要临床类型：溃疡性结肠炎和克罗恩病。目前IBD的治疗模式主要侧重于症状管理。然而，这种方法并不能支持黏膜上皮修复、维持屏障稳态或调节肠道生物功能。传统疗法依赖于频繁使用高剂量药物，包括抗生素、非甾体抗炎药、生物制剂和免疫调节剂。最近，间充质干/基质细胞（MSCs）因其独特的分化和分泌调节因子（包括细胞外囊泡（EVs））的能力而在组织再生方面受到关注，这些调节因子在异常组织形成中起关键作用。在临床前和临床研究中探索了多种给药途径，以递送来自不同组织来源的MSCs。这些途径包括腹腔内、静脉内和局部（结肠内或直肠内）给药。所使用的MSCs取自各种组织，包括骨髓、脐带和脂肪组织。本文综述了MSCs及其分泌的EVs在IBD治疗中的应用研究框架，强调了关键的免疫效应，如免疫微环境调节、肠道屏障稳定以及针对肠道屏障障碍的治疗方法。讨论主要集中在MSCs相对于其他生物制剂的优势、IBD发展过程中肠道黏膜组织驻留间充质干细胞的损伤、IBD框架内的免疫靶点（细胞和分子水平）以及MSCs在IBD微环境中的修复作用。我们旨在概述MSCs研究和治疗的当前趋势，并确定推进IBD的MSCs介导治疗策略研究必须解决的挑战和未来方向。
