Sodium Hydrosulfide Modification of Mesenchymal Stem Cell-Exosomes Improves Liver Function in CCL4-Induced Hepatic Injury in Mice.

IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Reports of Biochemistry and Molecular Biology Pub Date : 2023-01-01 DOI:10.52547/rbmb.11.4.644
Maryam Jafar Sameri, Rafeie Belali, Niloofar Neisi, Reza Noei Razliqi, Seyed Ali Mard, Feryal Savari, Seyyed Saeed Azandeh
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Abstract

Background: Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of Sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL4-induced acute liver injury to ascertain their role in ameliorating hepatic injury.

Methods: Human Mesenchymal stem cells (MSCs) were treated with or without NaHS (1 μmol) and exosomes were isolated using an exosome isolation kit. Male mice (8-12 weeks old) were randomly divided into four groups (n=6): 1-control, 2-PBS, 3- MSC-Exo, and 4- H2S-Exo. Animals received 2.8 ml/kg body weight of CCL4 solution intraperitoneally, and 24 h later MSC-Exo (non-modified), H2S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, 24 h after Exo administration, mice were sacrificed for tissue and blood collection.

Results: Administration of both MSC-Exo and H2S-Exo reduced inflammatory cytokines (IL-6, TNF-α), total oxidant levels, liver aminotransferases, and cellular apoptosis.

Conclusion: MSC-Exo and H2S-Exo had hepato-protective effects against CCL4-induced liver injury in mice. Modification of cell culture medium with NaHS as an H2S donor enhances the therapeutic effects of MSC exosomes.

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氢硫化钠修饰间充质干细胞外泌体改善ccl4诱导肝损伤小鼠肝功能
背景:肝脏疾病和损伤是世界范围内重要的医学问题。急性肝衰竭(Acute liver failure, ALF)是一种以肝细胞严重功能损害和广泛死亡为特征的临床综合征。肝移植是目前唯一可行的治疗方法。外泌体是起源于胞内细胞器的纳米囊泡。它们调节受体细胞的细胞和分子机制,在急性和慢性肝损伤的临床应用中具有良好的潜力。本研究比较了氢硫化钠修饰的外泌体和未修饰的外泌体在ccl4诱导的急性肝损伤中的作用,以确定它们在改善肝损伤中的作用。方法:用NaHS (1 μmol)处理或不处理人间充质干细胞(MSCs),采用外泌体分离试剂盒分离外泌体。8 ~ 12周龄雄性小鼠随机分为4组(n=6): 1-对照、2-PBS、3- MSC-Exo、4- H2S-Exo。动物腹腔注射2.8 ml/kg体重的CCL4溶液,24 h后尾静脉注射MSC-Exo(未修饰)、H2S-Exo (nahs修饰)或PBS。在给药24 h后处死小鼠进行组织和血液采集。结果:MSC-Exo和H2S-Exo均可降低炎症因子(IL-6、TNF-α)、总氧化剂水平、肝脏转氨酶和细胞凋亡。结论:MSC-Exo和H2S-Exo对ccl4诱导的小鼠肝损伤具有保护作用。以NaHS作为H2S供体修饰细胞培养基,增强MSC外泌体的治疗效果。
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来源期刊
Reports of Biochemistry and Molecular Biology
Reports of Biochemistry and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.80
自引率
23.50%
发文量
60
审稿时长
10 weeks
期刊介绍: The Reports of Biochemistry & Molecular Biology (RBMB) is the official journal of the Varastegan Institute for Medical Sciences and is dedicated to furthering international exchange of medical and biomedical science experience and opinion and a platform for worldwide dissemination. The RBMB is a medical journal that gives special emphasis to biochemical research and molecular biology studies. The Journal invites original and review articles, short communications, reports on experiments and clinical cases, and case reports containing new insights into any aspect of biochemistry and molecular biology that are not published or being considered for publication elsewhere. Publications are accepted in the form of reports of original research, brief communications, case reports, structured reviews, editorials, commentaries, views and perspectives, letters to authors, book reviews, resources, news, and event agenda.
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