The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum Stress
Background: Due to the scarcity of treatment options, managing the progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to cirrhosis necessitates innovative approaches. This study focused on endoplasmic reticulum (ER) stress, apoptosis, and autophagy as key mechanisms in NAFLD pat...
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Shiraz University of Medical Sciences
2025-05-01
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| Series: | Iranian Journal of Medical Sciences |
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| Online Access: | https://ijms.sums.ac.ir/article_50757_7527c43e82dd45e57bdf82265506acff.pdf |
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| author | Zahra Moayedfard Kamran Lankarani Ali Akbar Alizadeh Ali Akbar Nekooeian Mahintaj Dara Farhad Koohpeyma Shima Parsa Saman Nikeghbalian Arghavan Hosseinpouri Negar Azarpira |
| author_facet | Zahra Moayedfard Kamran Lankarani Ali Akbar Alizadeh Ali Akbar Nekooeian Mahintaj Dara Farhad Koohpeyma Shima Parsa Saman Nikeghbalian Arghavan Hosseinpouri Negar Azarpira |
| author_sort | Zahra Moayedfard |
| collection | DOAJ |
| description | Background: Due to the scarcity of treatment options, managing the progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to cirrhosis necessitates innovative approaches. This study focused on endoplasmic reticulum (ER) stress, apoptosis, and autophagy as key mechanisms in NAFLD pathogenesis. It also highlighted the potential of adipose-derived mesenchymal stem cells (AD-MSCs) and their exosomes as promising therapeutic options.Methods: The study was conducted at the Department of Regenerative Medicine, Shiraz University of Medical Sciences, (Shiraz, Iran) from November 2021 to December 2023. The mice (n=32) were divided into four groups: control, high-fat diet (HFD) without treatment, HFD with AD-MSCs treatment, and HFD with AD-MSCs-derived exosomes groups. The mice were fed HFD for 8 weeks. They received MSC and exosomes for the last 3 weeks. One week after the final injection, mice were tested for serum testing, stereological analysis, and real-time polymerase chain reaction (RT-PCR). The data were analyzed using the Graph-Pad Prism software by one-way analysis of variance (ANOVA) with Tukey analysis as a post hoc comparison between groups. P<0.05 indicated a significant difference. Results: AD-MSCs-exosomes significantly reduced ER stress indicators (IRE1α [P=0.0001], PERK [P=0.0006], ATF6 [P=0.0001], and GRP78 [P=0.0001]), apoptosis markers (Bax [P=0.005] and Cas3 [P=0.001]), and autophagic flux markers (P62 [P=0.0001] and LC3B/A [P=0.003]). Conclusion: In this investigation, AD-MSCs-exosomes significantly restored autophagy and suppressed unfolded protein response (UPR) pathways in the early stages of NAFLD. |
| format | Article |
| id | doaj-art-e832cc197070436e87b9ddf1d22a7c6b |
| institution | OA Journals |
| issn | 0253-0716 1735-3688 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Shiraz University of Medical Sciences |
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| series | Iranian Journal of Medical Sciences |
| spelling | doaj-art-e832cc197070436e87b9ddf1d22a7c6b2025-08-20T02:34:10ZengShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-07161735-36882025-05-0150533435010.30476/ijms.2024.103376.366050757The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum StressZahra Moayedfard0Kamran Lankarani1Ali Akbar Alizadeh2Ali Akbar Nekooeian3Mahintaj Dara4Farhad Koohpeyma5Shima Parsa6Saman Nikeghbalian7Arghavan Hosseinpouri8Negar Azarpira9Student Research Committee, Shiraz University of Medical Sciences, Shiraz, IranHealth Policy Research Center (HPRC), Shiraz University of Medical Sciences, Shiraz, Iran.Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranStem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, IranStudent Research Committee, Shiraz University of Medical Sciences, Shiraz, IranTransplant Research Center, Shiraz University of Medical Sciences, Shiraz, IranAbu Ali Sina Hospital for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, IranStudent Research Committee, Shiraz University of Medical Sciences, Shiraz, IranTransplant Research Center, Shiraz University of Medical Sciences, Shiraz, IranBackground: Due to the scarcity of treatment options, managing the progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to cirrhosis necessitates innovative approaches. This study focused on endoplasmic reticulum (ER) stress, apoptosis, and autophagy as key mechanisms in NAFLD pathogenesis. It also highlighted the potential of adipose-derived mesenchymal stem cells (AD-MSCs) and their exosomes as promising therapeutic options.Methods: The study was conducted at the Department of Regenerative Medicine, Shiraz University of Medical Sciences, (Shiraz, Iran) from November 2021 to December 2023. The mice (n=32) were divided into four groups: control, high-fat diet (HFD) without treatment, HFD with AD-MSCs treatment, and HFD with AD-MSCs-derived exosomes groups. The mice were fed HFD for 8 weeks. They received MSC and exosomes for the last 3 weeks. One week after the final injection, mice were tested for serum testing, stereological analysis, and real-time polymerase chain reaction (RT-PCR). The data were analyzed using the Graph-Pad Prism software by one-way analysis of variance (ANOVA) with Tukey analysis as a post hoc comparison between groups. P<0.05 indicated a significant difference. Results: AD-MSCs-exosomes significantly reduced ER stress indicators (IRE1α [P=0.0001], PERK [P=0.0006], ATF6 [P=0.0001], and GRP78 [P=0.0001]), apoptosis markers (Bax [P=0.005] and Cas3 [P=0.001]), and autophagic flux markers (P62 [P=0.0001] and LC3B/A [P=0.003]). Conclusion: In this investigation, AD-MSCs-exosomes significantly restored autophagy and suppressed unfolded protein response (UPR) pathways in the early stages of NAFLD.https://ijms.sums.ac.ir/article_50757_7527c43e82dd45e57bdf82265506acff.pdfnon-alcoholic fatty liver diseasemesenchymal stem cellsexosomeautophagyendoplasmic reticulum stress |
| spellingShingle | Zahra Moayedfard Kamran Lankarani Ali Akbar Alizadeh Ali Akbar Nekooeian Mahintaj Dara Farhad Koohpeyma Shima Parsa Saman Nikeghbalian Arghavan Hosseinpouri Negar Azarpira The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum Stress Iranian Journal of Medical Sciences non-alcoholic fatty liver disease mesenchymal stem cells exosome autophagy endoplasmic reticulum stress |
| title | The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum Stress |
| title_full | The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum Stress |
| title_fullStr | The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum Stress |
| title_full_unstemmed | The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum Stress |
| title_short | The Ameliorative Effect of Adipose-Derived Mesenchymal Stem Cells and Their Exosomes in Non-alcoholic Steatohepatitis by Simultaneously Enhancing Autophagic Flux and Suppressing Endoplasmic Reticulum Stress |
| title_sort | ameliorative effect of adipose derived mesenchymal stem cells and their exosomes in non alcoholic steatohepatitis by simultaneously enhancing autophagic flux and suppressing endoplasmic reticulum stress |
| topic | non-alcoholic fatty liver disease mesenchymal stem cells exosome autophagy endoplasmic reticulum stress |
| url | https://ijms.sums.ac.ir/article_50757_7527c43e82dd45e57bdf82265506acff.pdf |
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