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Iranian Journal of Medical Sciences، جلد ۴۹، شماره ۱۱، صفحات ۷۲۴-۷۴۰
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عنوان انگلیسی Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221
چکیده انگلیسی مقاله Background: The therapeutic effect of mesenchymal stem cells (MSCs) in liver cirrhosis is limited by their entrapment in the pulmonary vessels. Thus, the use of MSC-derived exosomes has become a promising strategy. The current work aimed to compare the role of human umbilical cord blood-MSCs (hUCB-MSCs) and their derived exosomes in the alleviation of liver cirrhosis focusing on the role of miR-23b and miR-221 and their direct effectors in inflammatory and autophagic pathways. 
Methods: Rats were divided into six groups: normal controls (negative control), liver cirrhosis group (positive control), liver cirrhotic rats that received conditioned media, liver cirrhotic rats that received hUCB-MSCs, cirrhotic rats that received exosomes, and cirrhotic rats that received both hUCB-MSCs and exosomes. The messenger RNA expression of transforming growth factor-β (TGF-β), Matrix metalloproteinase 9 (MMP 9), fibronectin, collagen type-1 (col1), alpha-smooth muscle actin (α-SMA), Suppressor of Mothers Against Decapentaplegic (SMAD) 2 and 7, Beclin, P62, and light chain 3 (LC3) were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemical staining for Beclin, P62, and LC3 was performed. 
Results: The treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly downregulated miRNA-221, fibronectin, collagen I, α-SMA, Smad2 (P<0.001, for each), and P62 (P=0.032, P<0.001, P<0.001, respectively). Additionally, the treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly upregulated mTOR, Beclin, LC3, and Smad7 (P<0.001, for each) and miRNA-23 (P=0.021, P<0.001, P<0.001, respectively).
Conclusion: hUCB-MSCs and their derived exosomes ameliorated liver cirrhosis by anti-inflammatory and anti-fibrotic effects besides modulation of autophagy. The exosomes had a better improvement effect either alone or combined with hUCB-MSCs, as proved by improvement in liver function tests, and molecular, histopathological, and immunohistochemical profiles. 
کلیدواژه‌های انگلیسی مقاله stem cells,Exosomes,Liver cirrhosis,Gene expression,MicroRNAs
نویسندگان مقاله Somia H. Abd-Allah |
Department of Medical Biochemistry and Molecular Biology, School of Medicine, Zagazig University, Zagazig, Egypt

Tarek Khamis |
Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt

Walaa Samy |
Department of Medical Biochemistry and Molecular Biology, School of Medicine, Zagazig University, Zagazig, Egypt

Amira Ebrahim Alsemeh |
Department of Anatomy, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Doaa M. Abdullah |
Department of Clinical Pharmacology , Faculty of Medicine, Zagazig University, Zagazig, Egypt

Samia Hussein |
Department of Medical Biochemistry and Molecular Biology, School of Medicine, Zagazig University, Zagazig, Egypt

نشانی اینترنتی https://ijms.sums.ac.ir/article_50173_85877c032e914208dcdef95108d01c96.pdf
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