Therapeutic effects of adipose tissue-derived mesenchymal stem cells on ER stress in a murine model of metabolic dysfunction-associated steatohepatitis: an in vivo and in vitro study.

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)

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasing concern due to lifestyle changes, with metabolic dysfunction-associated steatohepatitis (MASH) leading to progressive liver damage, cirrhosis, and increased morbidity. The role of endoplasmic reticulum (ER) stress, particularly the unfolded protein response (UPR) pathway, in MASH progression remains unclear. Adipose tissue-derived stem cells (ADSCs) have shown promise in regenerative therapy; however, their mechanism for alleviating MASH-induced liver damage is not fully understood. In this study, we aimed to investigate the therapeutic mechanism of ADSCs in MASH, focusing on their modulation of ER stress in hepatocytes. Methods C57BL/6J mice were fed either an atherogenic high-fat diet (AT + HF) or a high-fat diet (HFD-60) to induce MASH and simple steatosis (SS), respectively. Liver tissues were analyzed for gene expression, protein levels, and apoptotic markers using DNA microarray, quantitative PCR, western blotting, histological staining, and caspase activity assays. ADSCs were harvested, cultured, and treated to assess their effects on ER stress. In vitro experiments investigated palmitic acid-induced ER stress in hepatocytes and the effects of ADSCs on hepatic stellate cells and inflammatory markers. Results The PERK arm of the UPR pathway was significantly upregulated in MASH liver

Evidence level

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

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