Dai Qiangqiang, Zhu Di, Du Xiaoming, Tan Hao, Chen Qiu
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Lipids Health Dis. 2025 Jun 19;24(1):217. doi: 10.1186/s12944-025-02635-1.
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.
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.
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.
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.
非酒精性脂肪性肝病（NAFLD）是一项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-EVs）已成为一种有前景的NAFLD治疗方法；然而，目前的证据仅限于临床前研究。本系统评价和荟萃分析评估了MSC-EVs在NAFLD及其进展形式非酒精性脂肪性肝炎（NASH）啮齿动物模型中的治疗效果。通过综合临床前数据，我们旨在建立一个可靠的证据基础，以指导未来的临床试验并优化基于MSC-EV的治疗方法。
全面检索PubMed、Web of Science、Embase、中国知网、万方和维普数据库，以确定符合条件的动物研究。通过SYRCLE偏倚风险工具评估方法学质量。根据Cochrane手册指南，使用Stata 18.0进行荟萃分析。
MSC-EVs可显著降低关键代谢参数，包括谷草转氨酶（SMD=-2.79，95%CI[-3.64，-1.94]，p<0.01）、谷丙转氨酶（SMD=-2.47，95%CI[-3.44，-1.50]，p<0.01）、甘油三酯（SMD=-1.86，95%CI[-2.98，-0.73]，P<0.01）、肝脏甘油三酯（SMD=-4.02，95%CI[-5.84，-2.20]，p<0.01）、总胆固醇（SMD=-2.52，95%CI[-3.56，-1.48]，p<0.01）、肝脏总胆固醇（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）、空腹血糖（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-EVs还改善了炎性细胞因子（TNF-α和IL-6）水平以及氧化应激标志物（SOD和MDA）。这些效果超过了先前针对肝病的MSC-EVs研究报告的效果，特别是在未评估的脂质参数和氧化应激指标方面。
MSC-EVs在治疗NAFLD/NASH方面显示出有前景的潜力，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，如人源细胞外囊泡、超过四周的治疗持续时间以及通过差速超速离心获得的外泌体制剂，直接为临床试验设计提供了参考，以最大限度地提高治疗效果。这些发现值得进一步的临床研究，以促进将MSC-EVs作为NAFLD/NASH的一种治疗选择进行临床转化。
