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Exosomes of Mesenchymal Stem Cells stimulated by Lipopolysaccharide can alleviate and treat Nonalcoholic Fatty Liver Disease in High Fat Diet-Fed Rats. Introducing a new remedy
Exosomes of Mesenchymal Stem Cells stimulated by Lipopolysaccharide can alleviate and treat Nonalcoholic Fatty Liver Disease in High Fat Diet-Fed Rats. Introducing a new remedy
Elham Shakerian,1,*Mojtaba Rashidi,2samane salehipoor,3akram ahangarpoor,4
1. 1-Department of Clinical Biochemistry, Faculty of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2-Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2. Department of Clinical Biochemistry, Faculty of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 3. Department of Clinical Biochemistry, Faculty of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 4. Department of physiology, Faculty of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Introduction: Nonalcoholic fatty liver disease, called NAFLD, is a liver disease in which too much fat builds up in the liver. Because of high-calorie and fat diets in most people, NAFLD is a common disease in the world and is associated with an elevated triglyceride level. However, there is currently no effective treatment for NAFLD.
Mesenchymal stem cells (MSCs) are long-lived cells with self-renewal capabilities, and they may have promising treatment potential for NAFLD.MSCs can be obtained from various sources, but adipose-derived stem cells (ADSCs) have better abilities to repair different tissues.
Exosomes are small extracellular membrane vesicles that contain proteins and nucleic acids to regulate intracellular signaling pathways, which are secreted by cells such as MSCs. The side effects of cell therapy will be reduced if we use exosomes instead. Exosomes have advantages over MSCs, like being smaller, less complex, more easily produced and stored. So, exosomes can be considered as an ideal therapeutic tool for diseases soon.
Lipopolysaccharide (LPS), a component of the cell walls of gram-negative bacteria, stimulates cells that contribute to inflammatory responses. Recent studies suggest that LPS-stimulated MSCs may release anti-inflammatory cytokines during inflammation.
Due to the high prevalence of NAFLD in the world and the absence of effective and safe remedies, finding a way to treat it is crucial. This study investigated the effect and comparison of Exosomes of Mesenchymal Stem Cells stimulated by Lipopolysaccharide (E +MSCs+L) and Exosomes of Mesenchymal Stem Cells not stimulated (E +MSCs) on NAFLD Treatment in High-Fat Diet-Fed Rats.
Methods: The inguinal adipose tissues of 7-week-old rats were isolated, and the Isolation and cultivation of Adipose-derived mesenchymal Stem Cells (ADSCs) and then Exosomes were done according to the protocol.
Male Wistar rats were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD. The rats were then categorized into 3 groups: The first group was treated with (E +MSCs+L), the second group was treated with (E +MSCs), and the last group was treated with nothing as a control group. Biochemical Measurements, including Liver enzymes (Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipidemic biochemistry factors, including high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), Triglyceride (TG), and cholesterol (Cho) were assessed using the Roche 6000 autoanalyzer.
The expression of genes, such as SREBP-1 and ACC (prolipogenic factors), PPARα and CPT-1(factors which increase β-oxidation), IL-6, IL-1β, and TGF-β (inflammation factors) were examined using real-time polymerase chain reaction (PCR). Histopathological examination was also done by a skilled liver pathologist to investigate liver injuries in each group.
Results: Rats fed with (HFD) showed a significant increase in body weight and liver triglyceride level compared to the control group.
(E + MSCs+ L) group was more effective in regulating body weight and reducing liver triglyceride levels than (E +MSCs) group. Treatment with (E + MSCs+ L) effectively amended liver enzymes (ALT and AST), and lipid factors, including Cho, TG, LDL-C, and HDL-C values, better than treatment with (E +MSCs) group. Treatment with (E +MSCs +L) significantly decreased factors associated with inflammatory responses (IL-6, TGF-β, IL-1β) and prolipogenic genes (SREBP-1 and ACC). Also, there was a significant increase in genes that upregulated β-oxidation (PPARα and CPT-1) in the rats treated with (E +MSCs+L) compared to those treated with (E +MSCs).
Conclusion: In this study, the NAFLD rats model were employed to assess the efficacy of (E + MSCs + L), compared to (E + MSCs). In two groups, exosomes could reduce NAFLD, but the effects of (E +MSCs +L) were more predominant. It shows that stimulating MSCs can produce more effective exosomes, which can further reduce and treat NAFLD. Treatment with (E + MSCs + L) showed potential effects in alleviating NAFLD by reducing the biomarkers of liver injury, lipid factors, and inflammatory genes in HFD rats compared to treatment with (E + MSCs). So, according to these data, Exosomes of Mesenchymal Stem Cells stimulated by Lipopolysaccharide (E + MSCs +L) can be introduced as an effective factor and new remedy for NAFLD treatment.