Somia H Abd-Allah, Tarek Khamis, Walaa Samy, Amira Ebrahim Alsemeh, Doaa M Abdullah, Samia Hussein
{"title":"间充质干细胞及其衍生的外泌体通过改变miR-23b和miR-221的表达缓解大鼠的肝硬化","authors":"Somia H Abd-Allah, Tarek Khamis, Walaa Samy, Amira Ebrahim Alsemeh, Doaa M Abdullah, Samia Hussein","doi":"10.30476/ijms.2023.99524.3159","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 <i>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</i> and <i>7, Beclin, P62,</i> and <i>light chain 3 (LC3)</i> were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemical staining for Beclin, P62, and LC3 was performed.</p><p><strong>Results: </strong>The treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly downregulated <i>miRNA-221, fibronectin, collagen I, α-SMA, Smad2</i> (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 <i>mTOR</i>, <i>Beclin</i>, <i>LC3</i>, and <i>Smad7</i> (P<0.001, for each) and <i>miRNA-23</i> (P=0.021, P<0.001, P<0.001, respectively).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14510,"journal":{"name":"Iranian Journal of Medical Sciences","volume":"49 11","pages":"724-740"},"PeriodicalIF":1.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645418/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221.\",\"authors\":\"Somia H Abd-Allah, Tarek Khamis, Walaa Samy, Amira Ebrahim Alsemeh, Doaa M Abdullah, Samia Hussein\",\"doi\":\"10.30476/ijms.2023.99524.3159\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 <i>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</i> and <i>7, Beclin, P62,</i> and <i>light chain 3 (LC3)</i> were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemical staining for Beclin, P62, and LC3 was performed.</p><p><strong>Results: </strong>The treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly downregulated <i>miRNA-221, fibronectin, collagen I, α-SMA, Smad2</i> (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 <i>mTOR</i>, <i>Beclin</i>, <i>LC3</i>, and <i>Smad7</i> (P<0.001, for each) and <i>miRNA-23</i> (P=0.021, P<0.001, P<0.001, respectively).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":14510,\"journal\":{\"name\":\"Iranian Journal of Medical Sciences\",\"volume\":\"49 11\",\"pages\":\"724-740\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645418/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Iranian Journal of Medical Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.30476/ijms.2023.99524.3159\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Medical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.30476/ijms.2023.99524.3159","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221.
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.
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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