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

被引：0
作者：
Abd-Allah, Somia H. [1 ]
Khamis, Tarek [2 ]
Samy, Walaa [1 ]
Alsemeh, Amira Ebrahim [3 ]
Abdullah, Doaa M. [4 ]
Hussein, Samia [1 ]
机构：
[1] Zagazig Univ, Sch Med, Dept Med Biochem & Mol Biol, Zagazig, Egypt
[2] Zagazig Univ, Fac Vet Med, Dept Pharmacol, Zagazig, Egypt
[3] Zagazig Univ, Fac Med, Dept Anat, Zagazig, Egypt
[4] Zagazig Univ, Fac Med, Dept Clin Pharmacol, Zagazig, Egypt
来源：
IRANIAN JOURNAL OF MEDICAL SCIENCES | 2024年 / 49卷 / 11期
关键词：
Stem cells; Exosomes; Liver cirrhosis; Gene expression; microRNAs; EXTRACELLULAR VESICLES; LIVER FIBROSIS; FAILURE;
D O I：
10.30476/ijms.2023.99524.3159
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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 (hUCBMSCs) 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-beta (TGF-beta), Matrix metalloproteinase 9 (MMP 9), fibronectin, collagen type-1 (col1), alpha-smooth muscle actin (alpha-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 Results: The treatment of cirrhotic rats with hUCB-MSCs, exosomes, orthe combination ofthem significantly downregulated miRNA-221, fibronectin, collagen I, alpha-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 miRNAConclusion: 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 hUCBMSCs, as proved by improvement in liver function tests, and molecular, histopathological, and immunohistochemical profiles.
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页码：724 / 740
页数：17
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