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.
Zahra Moayedfard, Kamran Bagheri Lankarani, Ali Akbar Alizadeh, Ali Akbar Nekooeian, Mahintaj Dara, Farhad Koohpeyma, Shima Parsa, Saman Nikeghbalian, Arghavan Hosseinpouri, Negar Azarpira
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Abstract
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.
期刊介绍：
The Iranian Journal of Medical Sciences (IJMS) is an international quarterly biomedical publication, which is sponsored by Shiraz University of Medical Sciences. The IJMS intends to provide a scientific medium of communication for researchers throughout the globe. The journal welcomes original clinical articles as well as clinically oriented basic science research experiences on prevalent diseases in the region and analysis of various regional problems.
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