Abd-Allah Somia H, Khamis Tarek, Samy Walaa, Alsemeh Amira Ebrahim, Abdullah Doaa M, Hussein Samia
Department of Medical Biochemistry and Molecular Biology, School of Medicine, Zagazig University, Zagazig, Egypt.
Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
Iran J Med Sci. 2024 Nov 1;49(11):724-740. doi: 10.30476/ijms.2023.99524.3159. eCollection 2024 Nov.
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.
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 and and were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemical staining for Beclin, P62, and LC3 was performed.
The treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly downregulated (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 , , , and (P<0.001, for each) and (P=0.021, P<0.001, P<0.001, respectively).
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.
间充质干细胞（MSCs）在肝硬化治疗中的效果受到其滞留在肺血管中的限制。因此，使用MSC来源的外泌体已成为一种有前景的策略。当前研究旨在比较人脐带血间充质干细胞（hUCB-MSCs）及其衍生外泌体在减轻肝硬化方面的作用，重点关注miR-23b和miR-221及其在炎症和自噬途径中的直接效应分子的作用。
将大鼠分为六组：正常对照组（阴性对照）、肝硬化组（阳性对照）、接受条件培养基的肝硬化大鼠、接受hUCB-MSCs的肝硬化大鼠、接受外泌体的肝硬化大鼠以及接受hUCB-MSCs和外泌体的肝硬化大鼠。通过定量实时聚合酶链反应评估 、 和 的信使核糖核酸表达。进行Beclin、P62和LC3的免疫组织化学染色。
用hUCB-MSCs、外泌体或它们的组合治疗肝硬化大鼠可显著下调 （每组P<0.001）和P62（分别为P=0.032、P<0.001、P<0.001）。此外，用hUCB-MSCs、外泌体或它们的组合治疗肝硬化大鼠可显著上调 、 、 和 （每组P<0.001）以及 （分别为P=0.021、P<0.001、P<0.001）。
hUCB-MSCs及其衍生外泌体除了调节自噬外，还通过抗炎和抗纤维化作用改善肝硬化。外泌体单独或与hUCB-MSCs联合使用具有更好的改善效果，这在肝功能测试以及分子、组织病理学和免疫组织化学分析中得到了证实。
