Therapeutic potential of mesenchymal stem cell-derived extracellular vesicle in nonalcoholic fatty liver disease: a systematic review and meta-analysis of preclinical evidence.

IF 3.9 2区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Lipids in Health and Disease Pub Date : 2025-06-19 DOI:10.1186/s12944-025-02635-1

Qiangqiang Dai, Di Zhu, Xiaoming Du, Hao Tan, Qiu Chen

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引用次数: 0

Abstract

Objective: Nonalcoholic fatty liver disease (NAFLD) is a global chronic health challenge, demanding the development of innovative therapeutic strategies. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic approach for NAFLD; however, current evidence is limited to preclinical studies. This systematic review and meta-analysis assessed the therapeutic efficacy of MSC-EVs in rodent models of NAFLD and its progressive form, nonalcoholic steatohepatitis (NASH). By synthesizing preclinical data, we aim to establish a robust evidence base that can guide future clinical trials and optimize MSC-EV-based therapies.

Methods: Comprehensive searches of the PubMed, Web of Science, Embase, CNKI, Wanfang, and VIP databases identified eligible animal studies. Methodological quality was assessed via the SYRCLE risk-of-bias tool. The meta-analyses were conducted following Cochrane Handbook guidelines via Stata 18.0.

Results: MSC-EVs led to significant reductions in key metabolic parameters, including AST (SMD = -2.79, 95% CI [-3.64, -1.94], p< 0.01), ALT (SMD = -2.47, 95% CI [-3.44, -1.50], p < 0.01), TG (SMD = -1.86, 95% CI [-2.98, -0.73], P < 0.01), liver TG (SMD = -4.02, 95% CI [-5.84, -2.20], p < 0.01), TC (SMD = -2.52, 95% CI [-3.56, -1.48], p < 0.01), liver TC (SMD = -5.28, 95% CI [-7.71, -2.84], p < 0.01), NAS score(SMD = -3.56, 95% CI [-5.04, -2.09], P < 0.01), FBG SMD = -1.89, 95% CI [-2.94, -0.83], p < 0.01), and body weight (SMD = -2.34, 95% CI [-3.94, -0.74], p < 0.01). Additionally, MSC-EVs improved the level of inflammatory cytokines (TNF-α and IL-6) and oxidative stress markers (SOD and MDA). These effects surpass those reported in previous MSC-EVs studies targeting liver disease, particularly regarding unassessed lipid parameters and oxidative stress indicators.

Conclusion: MSC-EVs show promising potential for treating NAFLD/NASH, with substantial evidence supporting their therapeutic and reparative effects. Our findings directly inform clinical trial design by identifying optimal parameters-such as human-derived EVs, treatment durations longer than four weeks, and exosome preparations obtained via differential ultracentrifugation-to maximize therapeutic efficacy. These findings warrant further clinical investigation to facilitate the clinical translation of MSC-EVs as a therapeutic option for NAFLD/NASH.

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间充质干细胞来源的细胞外囊泡治疗非酒精性脂肪肝的潜力：临床前证据的系统回顾和荟萃分析

目的：非酒精性脂肪性肝病（NAFLD）是一种全球性的慢性健康挑战，需要开发创新的治疗策略。间充质基质细胞衍生的细胞外囊泡（msc - ev）已成为NAFLD的一种有前景的治疗方法；然而，目前的证据仅限于临床前研究。本系统综述和荟萃分析评估了msc - ev对NAFLD及其进展型非酒精性脂肪性肝炎（NASH）啮齿动物模型的治疗效果。通过综合临床前数据，我们的目标是建立一个强有力的证据基础，可以指导未来的临床试验和优化基于msc - ev的治疗方法。方法：综合检索PubMed、Web of Science、Embase、CNKI、万方、VIP等数据库，确定符合条件的动物研究。通过sycle偏倚风险工具评估方法学质量。meta分析遵循Cochrane Handbook指南，通过Stata 18.0进行。结果:MSC-EVs导致显著减少关键代谢参数,包括AST (SMD = -2.79, 95% CI [-3.64, -1.94], p < 0.01), ALT (SMD = -2.47, 95% CI [-3.44, -1.50], p < 0.01), TG (SMD = -1.86, 95% CI [-2.98, -0.73], p < 0.01),肝脏TG (SMD = -4.02, 95% CI [-5.84, -2.20], p < 0.01), TC (SMD = -2.52, 95% CI [-3.56, -1.48], p < 0.01),肝脏TC (SMD = -5.28, 95% CI [-7.71, -2.84], p < 0.01), NAS评分(SMD = -3.56, 95% CI [-5.04, -2.09], p < 0.01),光纤光栅SMD = -1.89, 95% CI [-2.94, -0.83],p < 0.01)和体重(SMD = -2.34, 95% CI [-3.94, -0.74], p < 0.01)。此外，msc - ev还能提高炎症因子（TNF-α和IL-6）和氧化应激标志物（SOD和MDA）的水平。这些效果超过了先前针对肝脏疾病的msc - ev研究中报道的效果，特别是在未评估的脂质参数和氧化应激指标方面。结论：msc - ev在治疗NAFLD/NASH方面具有良好的潜力，有大量证据支持其治疗和修复作用。我们的研究结果通过确定最佳参数（如人源性ev，治疗时间超过四周，以及通过差示超离心获得的外泌体制剂）直接为临床试验设计提供信息，以最大限度地提高治疗效果。这些发现需要进一步的临床研究，以促进msc - ev作为NAFLD/NASH治疗选择的临床转化。

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来源期刊

Lipids in Health and Disease 生物-生化与分子生物学

CiteScore

7.70

自引率

2.20%

发文量

122

审稿时长

3-8 weeks

期刊介绍： Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.