مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
Lipopolysaccharide-stimulated adipose-derived Mesenchymal Stem Cells have the potential effect to treat Nonalcoholic fatty liver disease in HFD-Fed Rats in comparison to AD-MSCs and fenofibrate
Lipopolysaccharide-stimulated adipose-derived Mesenchymal Stem Cells have the potential effect to treat Nonalcoholic fatty liver disease in HFD-Fed Rats in comparison to AD-MSCs and fenofibrate
Elham Shakerian,1,*
1. 1-Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2-Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Introduction: introduction: Nonalcoholic fatty liver disease, often called NAFLD, is a liver problem in which too much fat builds up in the liver. It is seen most often in people who are overweight or obese. Because of high-caloric and fat diets in most people, NAFLD is common in the world and is associated with an elevated triglyceride level. It is the most common form of liver disease in the world. However, there is currently no effective treatment for NAFLD. Fenofibrate (FENO) is a first-line medication commonly used to lower triglyceride levels. Fenofibrate contributes to the regulation of carbohydrate and lipid metabolism. However, it may also increase the excretion of cholesterol from bile, which can increase the risk of developing gallstones so it is not completely safe.
Mesenchymal stem cells (MSCs) are long-lived cells with self-renewal capability, and they may have an optimistic treatment potential for NAFLD.MSCs can be obtained from various sources, including bone marrow, adipose tissue, and umbilical cord. Among them, adipose-derived stem cells (ADSCs) have gained attention for their potential repair of various tissues.
Lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, is likely to stimulate cells that contribute to inflammatory responses (such as macrophages and neutrophils) and pro-inflammatory factors (such as IL-1β, IL-6, and TNF-α). 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 lipopolysaccharide (LPS)--stimulated adipose-derived stem cells (ADSCs), adipose-derived stem cells, and fenofibrate on NAFLD Treatment in High-Fat Diet-Fed Rats.
Methods: method: The inguinal adipose tissues of 7-week-old rats were isolated, and the Isolation and cultivation of Adipose-derived mesenchymal Stem Cells (ADSCs) according to protocol was done. 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 adipose-derived stem cells (ADSCs), the second group was treated with LPS+ADSCs, and the last group was treated with fenofibrate (FENO) (as standard therapy group) groups. Liver and body weight were measured. Biochemical Measurements including Liver enzymes (Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) lipid profiles were assessed using the Roche 6000 autoanalyzer.
The expression of genes, such as IL-6, IL-1β, TNF-α, TGF-β, monocyte chemoattractant protein 1 (MCP-1), and the expression of genes involved in fatty acid biosynthesis, β-oxidation, and inflammation were examined using real-time polymerase chain reaction (PCR). Histopathological Examination also was done by a skilled liver pathologist to investigate liver injuries in each group
Results: results: Rats fed with a high-fat emulsion for 12 weeks exhibited a significant increase in body weight, liver weight, and liver triglyceride compared to the normal control group.
Lipopolysaccharide-stimulated Adipose-derived mesenchymal Stem Cells (LPS+ADSCs) were more effective in regulating liver and body weight and reducing liver triglyceride levels than the other groups. Treatment with Lipopolysaccharide -stimulated ADSCs effectively amended liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and lipid factors, including LDL-C and HDL-C values, better than treatment with both FENO and MSCs. ADSCs + LPS treatment significantly decreased genes associated with inflammatory responses (IL-6, TNFα, TGF-β, IL-1β). Also, there was a significant reduction in reactive oxygen species (ROS) levels in the rats treated with ADSCs + LPS.
Conclusion: conclusion:In this study, the NAFLD rats model induced by a high-fat diet were employed to assess the efficacy of Lipopolysaccharide -stimulated ADSCs, compared to ADSCs alone and FENO, a widely used hypolipidemic drug for dyslipidemia treatment. Lipopolysaccharide-stimulated ADSCs showed potential effects in alleviating NAFLD by reducing the biomarkers of liver injury (ALT and AST), lipid factors (including HDL-C and LDL-C), inflammatory genes (IL-6, TNFα, TGF-β, IL-1β) and ROS levels in HFD rats than treatment with ADSCs and FENO groups. Additionally, ADSCs stimulated with LPS exhibit a significant reduction in NAFLD characteristics and are more effective than ADSCs alone and FENO so Lipopolysaccharide-stimulated ADSCs can be introduced as an effective remedy for NAFLD treatment in medicine.