Mesenchymal stem cell-derived apoptotic vesicles regulate irritable bowel syndrome in mice via the 5-HT brain-gut axis.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-07-01 DOI:10.1186/s13287-025-04448-6

Ya Sun, Di Wu, Lu Lu, Jinyang Wang, Xuanyi Li, Xueli Mao, Yijun Zhang

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Abstract

Background: Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal disorder characterized by abnormal brain-gut interactions. The pathogenic mechanisms of IBS are not fully understood, and current treatments are limited in efficacy.

Aims: This study aims to investigate the potential therapeutic effects of mesenchymal stem cell-derived apoptotic vesicles (apoVs) on IBS in a mouse model, focusing on their impact on the 5-HT brain-gut axis.

Methods: We extracted and characterized apoVs from adipose-derived stem cells (ADSCs, Mesenchymal stem cells derived from adipose) induced to undergo apoptosis. IBS was induced in C57BL/6 mice using a chronic stress model. Mice were treated with apoVs via tail vein injection, and various behavioral, physiological, and biochemical parameters were assessed.

Results: IBS patients exhibited increased circulating vesicles in peripheral blood, correlating with brain functional activity. Further animal studies found that apoVs treatment in IBS mice reduced 5-HT levels in the brain and gut, alleviated symptoms such as slowed weight gain and visceral hypersensitivity, and restored intestinal barrier function. Additionally, apoVs improved neuronal activation and mucin secretion in the gut.

Conclusions: Our findings suggest that apoVs act as novel messengers in brain-gut axis interactions, regulating brain-gut homeostasis. This study provides a new therapeutic approach for the treatment of functional gastrointestinal disorders like IBS.

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间充质干细胞衍生的凋亡囊泡通过5-HT脑-肠轴调节小鼠肠易激综合征。

背景：肠易激综合征（IBS）是一种常见的以脑-肠相互作用异常为特征的功能性胃肠道疾病。肠易激综合征的致病机制尚不完全清楚，目前的治疗方法疗效有限。目的：本研究旨在探讨间充质干细胞来源的凋亡囊泡（apoVs）对小鼠IBS模型的潜在治疗作用，重点研究其对5-HT脑肠轴的影响。方法：从诱导凋亡的脂肪源性干细胞（ADSCs，来源于脂肪的间充质干细胞）中提取并鉴定载脂蛋白。采用慢性应激模型诱导C57BL/6小鼠肠易激综合征。小鼠经尾静脉注射apoVs，观察其行为、生理和生化指标。结果：IBS患者外周血循环囊泡增加，与脑功能活动相关。进一步的动物研究发现，在IBS小鼠中，apoVs治疗降低了大脑和肠道中的5-HT水平，减轻了体重增加缓慢和内脏过敏等症状，并恢复了肠道屏障功能。此外，apoVs改善了肠道内的神经元激活和粘蛋白分泌。结论：我们的研究结果表明，apov在脑-肠轴相互作用中作为新的信使，调节脑-肠稳态。本研究为肠易激综合征等功能性胃肠疾病的治疗提供了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.