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Objective <p>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.</p> Methods <p>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.</p> Results <p>MSC-EVs led to significant reductions in key metabolic parameters, including AST (SMD = -2.79, 95% CI [-3.64, -1.94], <i>p</i>&lt; 0.01), ALT (SMD = -2.47, 95% CI [-3.44, -1.50], <i>p</i>&lt; 0.01),&#xa0;TG (SMD = -1.86, 95% CI [-2.98, -0.73], <i>P </i>&lt; 0.01), liver TG (SMD = -4.02, 95% CI [-5.84,&#xa0;-2.20], <i>p</i> &lt; 0.01), TC (SMD = -2.52, 95% CI [-3.56, -1.48], <i>p</i> &lt; 0.01), liver TC (SMD = -5.28,&#xa0;95% CI [-7.71,-2.84], <i>p</i> &lt; 0.01), NAS score(SMD = -3.56, 95% CI [-5.04, -2.09], <i>P </i>&lt; 0.01),&#xa0;FBG SMD = -1.89, 95% CI [-2.94, -0.83],<i> p</i> &lt; 0.01), and body weight (SMD = -2.34, 95% CI&#xa0;[-3.94, -0.74], <i>p</i> &lt; 0.01). Additionally, MSC-EVs improved the level of inflammatory&#xa0;cytokines (TNF-α and IL-6) and oxidative stress markers (SOD and MDA). These effects&#xa0;surpass those reported in previous MSC-EVs studies targeting liver disease, particularly&#xa0;regarding unassessed lipid parameters and oxidative stress indicators. </p> Conclusion <p>MSC-EVs show promising potential for treating NAFLD/NASH, with substantial evidence supporting their therapeutic and reparative effects. Our findings directly inform clinical trial&#xa0;design by identifying optimal parameters-such as human-derived EVs, treatment durations longer than four weeks, and exosome preparations obtained via differential&#xa0;ultracentrifugation-to maximize therapeutic efficacy. These findings warrant further clinical&#xa0;investigation to facilitate the clinical translation of MSC-EVs as a therapeutic option for NAFLD/NASH.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月19日

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

摘要

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.