Innovative mesenchymal stem cell treatments for fatty liver disease

The incidence of non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) is increasing year by year due to changes in the contemporary environment and dietary structure, and is an important public health problem worldwide. There is an urgent need to continuously improve the understanding of their disease mechanisms and develop novel therapeutic strategies. Mesenchymal stem cells (MSCs) have shown promise as a potential therapeutic strategy in therapeutic studies of NAFLD and ALD. NAFLD and ALD have different triggers and their specific mechanisms of disease progression are different, but both involve disease processes such as hepatocellular steatosis and potential fibrosis, cirrhosis, and even hepatocellular carcinoma. MSCs have metabolic regulatory, anti-apoptotic, antioxidant, and immunomodulatory effects that together promote liver injury repair and functional recovery, and have demonstrated positive results in preclinical studies. This editorial is a continuum of Jiang et al’s review focusing on the advantages and limitations of MSCs and their derivatives as therapeutics for NAFLD and ALD. They detail how MSCs attenuate the progression of NAFLD by modulating molecular pathways involved in glucolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. Based on recent advances, we discuss MSCs and their derivatives as therapeutic strategies for NAFLD and ALD, providing useful information for their clinical application.

Key Words: Alcohol-associated liver disease; Non-alcoholic fatty liver disease; Mesenchymal stem cells; Cell therapy; Inflammation

Core Tip: Mesenchymal stem cells (MSCs) and their derivatives are a promising therapeutic approach for non-alcoholic fatty liver disease and alcohol-associated liver disease. MSCs, which come from diverse sources and are of low immunogenicity, can attenuate disease progression by modulating key molecular pathways, such as glycolipid metabolism, inflammation, oxidative stress, and fibrosis. In addition, derivatives of MSCs are also considered as a therapeutic strategy due to their ability to retain some of the beneficial effects of MSCs while reducing the risks inherent in cell therapy. However, further studies are needed to emphasize their important mechanistic role in liver injury repair. Refining protocols for the clinical application of MSCs under the prerequisite of a well-defined mechanistic understanding may allow utilizing the full benefits of MSCs in the treatment of liver disease to enhance liver reparability and provide new hope for the treatment of non-alcoholic fatty liver disease and alcohol-associated liver disease.



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