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Review
. 2024 Jul 26;16(7):760-772.
doi: 10.4252/wjsc.v16.i7.760.

Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

Yan Jiang  1   2 , Narazah Mohd Yusoff  3 , Jiang Du  4   5 , Emmanuel Jairaj Moses  2 , Jun-Tang Lin  5   6
Affiliations
Review

Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

Yan Jiang et al. World J Stem Cells. .

Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents as benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, and minimal immunogenicity, positioning them as a therapeutic innovation for liver diseases. Therefore, this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics, and support the development of MSC-based therapy in the treatment of NAFLD.

Keywords: Endoplasmic reticulum stress; Fibrosis; Inflammation; Lipid accumulation; Mesenchymal stem cells; Non-alcoholic induced fatty liver disease; Oxidative stress.

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Conflict of interest statement

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Figures

Figure 1
Figure 1
The therapeutic efficacy of mesenchymal stromal/stem cells and mesenchymal stromal/stem cell-derived secretory factors in managing non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. Hepatic insulin resistance and lipid accumulation are exacerbated by multiple detrimental factors, resulting in hepatocyte damage. The transplantation of mesenchymal stem cells (MSCs) and their derived secretory factors introduces a holistic approach to liver health. These cells not only regulate lipid metabolism and enhance insulin sensitivity but also reduce fat accumulation in the liver. Their anti-inflammatory properties are emphasized by their ability to inhibit the activation of immune cells, such as Kupffer cells and natural killer cells, and by their role in reducing the secretion of pro-inflammatory cytokines. Additionally, MSCs produce antioxidants that neutralize reactive oxygen species in the liver, thereby mitigating both oxidative stress and endoplasmic reticulum stress. In countering liver fibrosis, MSCs play a prominent role by suppressing hepatic stellate cells, releasing anti-fibrotic factors, and aiding in hepatocytes repair. Moreover, these stem cells secrete cytokines that are crucial for liver tissue repair and regeneration. MSC: Mesenchymal stem cell; EVs: Extracellular vesicles; ER: Endoplasmic reticulum; ROS: Reactive oxygen species; HSC: Hepatic stellate cell.
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