Key result
Mesenchymal stem cell-derived extracellular vesicles significantly reduced AST levels (SMD -2.79) and other key metabolic parameters in rodent models of NAFLD and NASH compared to controls.
Why the study?
Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapy for nonalcoholic fatty liver disease, but current evidence is limited to preclinical studies.
Does mesenchymal stem cell-derived extracellular vesicle therapy improve metabolic, hepatic, and inflammatory biomarkers in preclinical rodent models of NAFLD and NASH?
Meta-Analysis (n=212)
Does mesenchymal stem cell-derived extracellular vesicle therapy improve metabolic, hepatic, and inflammatory biomarkers in preclinical rodent models of NAFLD and NASH?
MSC-EVs demonstrate significant therapeutic potential in preclinical rodent models of NAFLD/NASH by improving liver enzymes, lipid profiles, and inflammatory markers, supporting future clinical translation.
Answers are grounded in this paper and cite their sources.
Do not use MSC-EVs for NAFLD yet; leaves open human translation of this preclinical signal.
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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Dai et al. (2025) conducted a meta-analysis in Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) (n=212). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) vs. Untreated or vehicle control (PBS) was evaluated on Aspartate transaminase (AST) levels (SMD -2.79, 95% CI -3.64, -1.94, p=<0.01). Mesenchymal stem cell-derived extracellular vesicles significantly reduced AST levels (SMD -2.79) and other key metabolic parameters in rodent models of NAFLD and NASH compared to controls.
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