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Abd-Allah, Somia H., Khamis, Tarek, Samy, Walaa, Alsemeh, Amira Ebrahim, Abdullah, Doaa M., Hussein, Samia. (1403). Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221. سامانه مدیریت نشریات علمی, 49(11), 724-740. doi: 10.30476/ijms.2023.99524.3159
Somia H. Abd-Allah; Tarek Khamis; Walaa Samy; Amira Ebrahim Alsemeh; Doaa M. Abdullah; Samia Hussein. "Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221". سامانه مدیریت نشریات علمی, 49, 11, 1403, 724-740. doi: 10.30476/ijms.2023.99524.3159
Abd-Allah, Somia H., Khamis, Tarek, Samy, Walaa, Alsemeh, Amira Ebrahim, Abdullah, Doaa M., Hussein, Samia. (1403). 'Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221', سامانه مدیریت نشریات علمی, 49(11), pp. 724-740. doi: 10.30476/ijms.2023.99524.3159
Abd-Allah, Somia H., Khamis, Tarek, Samy, Walaa, Alsemeh, Amira Ebrahim, Abdullah, Doaa M., Hussein, Samia. Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221. سامانه مدیریت نشریات علمی, 1403; 49(11): 724-740. doi: 10.30476/ijms.2023.99524.3159

Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221

Iranian Journal of Medical Sciences
مقاله 6، دوره 49، شماره 11، بهمن 2024، صفحه 724-740    اصل مقاله (4.32 M)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2023.99524.3159
نویسندگان
Somia H. Abd-Allah1؛ Tarek Khamis2؛ Walaa Samy1؛ Amira Ebrahim Alsemeh3؛ Doaa M. Abdullah4؛ Samia Hussein* 1
1Department of Medical Biochemistry and Molecular Biology, School of Medicine, Zagazig University, Zagazig, Egypt
2Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
3Department of Anatomy, Faculty of Medicine, Zagazig University, Zagazig, Egypt
4Department of Clinical Pharmacology , Faculty of Medicine, Zagazig University, Zagazig, Egypt
چکیده
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. 
کلیدواژه‌ها
Stem cells؛ Exosomes؛ Liver cirrhosis؛ Gene expression؛ microRNAs
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