间充质干细胞衍生细胞外囊泡的治疗潜力:聚焦炎症性肠病。

IF 7.9 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Laura Clua-Ferré, Roger Suau, Irene Vañó-Segarra, Iris Ginés, Carolina Serena, Josep Manyé
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引用次数: 0

摘要

背景:间充质干细胞衍生的细胞外囊泡(MSC-EVs)已成为细胞间通讯的关键调节剂,通过向靶细胞输送生物活性货物来协调重要的生物过程。现有证据表明,间充质干细胞细胞外囊泡能模拟其亲代细胞的功能,表现出免疫调节、促进再生、抗凋亡和抗纤维化等特性。因此,间充质干细胞-EVs是炎症性肠病(IBD)患者的一种无细胞治疗选择,克服了细胞替代疗法的局限性,包括其非免疫原性、较低的致瘤风险、货物特异性以及易于操作和储存:本综述旨在全面探讨间充质干细胞-EVs在IBD中的疗效,重点关注其作用机制及其对治疗结果的潜在影响。我们研究了间充质干细胞-EV相对于传统疗法的优势,讨论了间充质干细胞-EV的分离和表征方法,并通过对间充质干细胞-EV载体进行转录组学、蛋白质组学和脂质组学分析,从机理上揭示了间充质干细胞-EV的治疗效果。我们还讨论了现有的临床前研究,这些研究表明间充质干细胞-EV 可在 IBD 模型中减轻炎症、促进组织修复和恢复肠道稳态,并将这些研究结果与临床试验结果进行了比较:最后,我们强调了间充质干细胞-EVs作为IBD新型疗法的潜力,并指出了将其转化为临床实践所面临的挑战和机遇:间充质干细胞(MSCs)的来源严重影响间充质干细胞衍生的细胞外囊泡(EVs)的组成和功能,从而影响其治疗潜力。源自脂肪的间充质干细胞胞外囊泡因其免疫调节特性和易于分离而闻名,有望治疗炎症性肠病(IBD)。微RNA在间充质干细胞-EV中始终存在于各种细胞类型中,并参与了IBD中失调的通路,使其成为潜在的治疗药物。例如,miR-let-7a 与抑制细胞凋亡有关,miR-100 支持细胞存活,miR-125b 帮助抑制促炎细胞因子,miR-20 促进抗炎 M2 巨噬细胞极化。对 IBD 模型的临床前研究表明,间充质干细胞-EV 可通过抑制促炎介质(如 TNF-α、IL-1β、IL-6)和增加抗炎因子(如 IL-4、IL-10)来减轻肠道炎症。它们还能促进粘膜愈合,加强肠道屏障的完整性,这表明它们具有解决 IBD 病理问题的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles: A focus on inflammatory bowel disease

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles: A focus on inflammatory bowel disease

Background

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as key regulators of intercellular communication, orchestrating essential biological processes by delivering bioactive cargoes to target cells. Available evidence suggests that MSC-EVs can mimic the functions of their parental cells, exhibiting immunomodulatory, pro-regenerative, anti-apoptotic, and antifibrotic properties. Consequently, MSC-EVs represent a cell-free therapeutic option for patients with inflammatory bowel disease (IBD), overcoming the limitations associated with cell replacement therapy, including their non-immunogenic nature, lower risk of tumourigenicity, cargo specificity and ease of manipulation and storage.

Main Topics Covered

This review aims to provide a comprehensive examination of the therapeutic efficacy of MSC-EVs in IBD, with a focus on their mechanisms of action and potential impact on treatment outcomes. We examine the advantages of MSC-EVs over traditional therapies, discuss methods for their isolation and characterisation, and present mechanistic insights into their therapeutic effects through transcriptomic, proteomic and lipidomic analyses of MSC-EV cargoes. We also discuss available preclinical studies demonstrating that MSC-EVs reduce inflammation, promote tissue repair and restore intestinal homeostasis in IBD models, and compare these findings with those of clinical trials.

Conclusions

Finally, we highlight the potential of MSC-EVs as a novel therapy for IBD and identify challenges and opportunities associated with their translation into clinical practice.

Highlights

  • The source of mesenchymal stem cells (MSCs) strongly influences the composition and function of MSC-derived extracellular vesicles (EVs), affecting their therapeutic potential. Adipose-derived MSC-EVs, known for their immunoregulatory properties and ease of isolation, show promise as a treatment for inflammatory bowel disease (IBD).
  • MicroRNAs are consistently present in MSC-EVs across cell types and are involved in pathways that are dysregulated in IBD, making them potential therapeutic agents. For example, miR-let-7a is associated with inhibition of apoptosis, miR-100 supports cell survival, miR-125b helps suppress pro-inflammatory cytokines and miR-20 promotes anti-inflammatory M2 macrophage polarisation.
  • Preclinical studies in IBD models have shown that MSC-EVs reduce intestinal inflammation by suppressing pro-inflammatory mediators (e.g., TNF-α, IL-1β, IL-6) and increasing anti-inflammatory factors (e.g., IL-4, IL-10). They also promote mucosal healing and strengthen the integrity of the gut barrier, suggesting their potential to address IBD pathology.
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来源期刊
CiteScore
15.90
自引率
1.90%
发文量
450
审稿时长
4 weeks
期刊介绍: Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
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