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Moayedfard, Zahra, Lankarani, Kamran, Alizadeh, Ali Akbar, Nekooeian, Ali Akbar, Dara, Mahintaj, Koohpeyma, Farhad, Parsa, Shima, Nikeghbalian, Saman, Hosseinpouri, Arghavan, Azarpira, Negar. (1404). 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. سامانه مدیریت نشریات علمی, 50(5), 334-350. doi: 10.30476/ijms.2024.103376.3660
Zahra Moayedfard; Kamran Bagheri 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". سامانه مدیریت نشریات علمی, 50, 5, 1404, 334-350. doi: 10.30476/ijms.2024.103376.3660
Moayedfard, Zahra, Lankarani, Kamran, Alizadeh, Ali Akbar, Nekooeian, Ali Akbar, Dara, Mahintaj, Koohpeyma, Farhad, Parsa, Shima, Nikeghbalian, Saman, Hosseinpouri, Arghavan, Azarpira, Negar. (1404). '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', سامانه مدیریت نشریات علمی, 50(5), pp. 334-350. doi: 10.30476/ijms.2024.103376.3660
Moayedfard, Zahra, Lankarani, Kamran, Alizadeh, Ali Akbar, Nekooeian, Ali Akbar, Dara, Mahintaj, Koohpeyma, Farhad, Parsa, Shima, Nikeghbalian, Saman, Hosseinpouri, Arghavan, Azarpira, Negar. 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. سامانه مدیریت نشریات علمی, 1404; 50(5): 334-350. doi: 10.30476/ijms.2024.103376.3660

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
مقاله 6، دوره 50، شماره 5، مرداد 2025، صفحه 334-350    اصل مقاله (3.56 M)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2024.103376.3660
نویسندگان
Zahra Moayedfard1، 2؛ Kamran Bagheri Lankarani3؛ Ali Akbar Alizadeh2؛ Ali Akbar Nekooeian4؛ Mahintaj Dara5؛ Farhad Koohpeyma1، 6؛ Shima Parsa7؛ Saman Nikeghbalian8؛ Arghavan Hosseinpouri1، 2؛ Negar Azarpira* 7
1Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
2Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
3Health Policy Research Center (HPRC), Shiraz University of Medical Sciences, Shiraz, Iran.
4Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
6Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
7Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
8Abu Ali Sina Hospital for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
چکیده
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.
کلیدواژه‌ها
Non-alcoholic fatty liver disease؛ Mesenchymal stem cells؛ Exosome؛ Autophagy؛ Endoplasmic reticulum stress
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