Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Currently, there are no approved drugs for treating non-alcoholic steatohepatitis (NASH); however, mesenchymal stem cells (MSCs) and their small extracellular vesicles (sEVs), which possess immunomodulatory activities, are potential candidates. This study aimed to develop a mouse model of NASH with rapid accumulation of fibrosis using the pre-established melanocortin type-4 receptor knockout ( Mc4r -KO) NASH mouse model and lipopolysaccharide (LPS), and to evaluate the therapeutic effect of MSCs and their sEVs. Methods Mc4r -KO mice (8 weeks old, male) were fed a western diet (WD) for 8 weeks. Next, the mice were intraperitoneally injected with lipopolysaccharide (LPS) twice a week for 4 weeks while continuing the WD. To confirm the therapeutic effect of MSCs and sEVs, human adipose tissue-derived MSCs or their sEVs were administered 12 weeks after initiation of the WD, and serum testing, quantitative analysis of fibrosis, and quantitative reverse transcription-polymerase chain reaction qRT-PCR were performed. Results By providing a WD combined with LPS treatment, we successfully developed a NASH model with rapid accumulation of fibrosis. Both human MSCs and their sEVs decreased serum alanine transaminase levels and inflammatory markers based on qRT-PCR. Histological analysis showed that MSC or sEV treatment did not affect fat accumulation. However, an improvement

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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