Pooled Analysis of Mesenchymal Stromal Cell-Derived Extracellular Vesicle Therapy for Liver Disease in Preclinical Models

Abstract

Background: Although increasing preclinical studies have emphasized the benefits of exosome-related therapies, the efficacy of mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) for liver injury is unclear. In this work, a pooled analysis was conducted to explore the overall effect of MSC-EV in animal models. Methods: A systematic search of the PubMed, EMBASE, Web of Science, and Cochrane Library databases was performed, from initiation to February 2022, for preclinical studies with liver disease models. The treatment outcomes were evaluated based on liver function, histological analysis, and inflammatory cytokines. Results: After screening, 39 studies were included. Pooled analyses demonstrated that MSC-EV therapy significantly improved liver functions (ALB, ALT, AST, ALP, and γ-GT), promoted the repair of injured liver tissue (damaged area, Ishak’s score), reduced inflammatory factors (TNF-α, IL-1β, IL-6, and IFN-γ), and increased an anti-inflammatory cytokine (IL-10) compared to the placebo control group. Subgroup analyses indicated that MSC-EV had therapeutic effects on liver fibrosis (n = 16), acute liver injury (n = 11), non-alcoholic fatty liver disease (n = 3), autoimmune hepatitis (n = 4), and hepatic ischemia-reperfusion injury (n = 6). Additionally, the therapeutic effect of EV was comparable to that of MSCs. Conclusion: MSC-EV have therapeutic potential for acute and chronic liver diseases.

Mesenchymal Stem Cell–Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?

“… 141 Exosomes derived from various MSCs have been used recently by researchers to treat various liver failure models, proving that they can protect against liver damage. 142 Yan et al 143 administered human umbilical cord MSC-derived exosomes (ucMSC-Ex) at low (8 mg/kg), medium (16 mg/kg), and high (32 mg/kg) doses to mice with carbon tetrachloride (CCl 4 )-induced liver failure. Large areas of steatosis and hepatocellular necrosis were found in the liver tissues of mice administered the low dose, whereas the liver tissue lesions in mice in the medium- and high-dose groups were significantly alleviated.…”