脂肪组织衍生间充质干细胞改变了阿尔茨海默氏症模型中脑胆固醇稳态的代谢产物

IF 1.7 4区 生物学 Q4 CELL BIOLOGY Cell Journal Pub Date : 2023-11-28 DOI:10.22074/cellj.2023.1999622.1272
Mehrnaz Karimi Darabi, Zahra Nazeri, Arash Rafeeinia, Seyedeh Pardis Pezeshki, Alireza Kheirollah, Yaghoob Farbood, Maryam Adelipour, Shirin Azizidoost, Maryam Cheraghzadeh
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引用次数: 0

摘要

目的:阿尔茨海默病(AD)中胆固醇平衡的破坏在疾病发病机制中起着至关重要的作用,使其成为一个潜在的治疗靶点。间充质干细胞(MSCs)有望治疗认知障碍,并提供了一种新的治疗方法。本研究旨在探讨间充质干细胞对AD大鼠模型中与脑胆固醇平衡相关的特定代谢物的影响:在这项实验研究中,动物被分为三组:对照组、AD 组和 AD+MSCs 组。使用淀粉样β(Aβ)诱导AD,并通过莫里斯水迷宫(MWM)行为测试和刚果红染色进行确认。提取间充质干细胞,通过流式细胞仪进行表征,对其进行成骨细胞和脂肪分化,然后将其注入脑室内。使用气相色谱-质谱联用仪(GC)-MS测定胆固醇代谢物水平,并在各组间进行比较:结果:与AD组相比,使用间充质干细胞治疗的AD+间充质干细胞组记忆功能明显改善,组织学评估显示β-淀粉样蛋白斑块数量减少。与对照组相比,AD组的脑胆固醇代谢物(包括去脂醇、7-脱氢胆固醇、24S-羟基胆固醇、27-羟基胆固醇和胆固醇)出现了紊乱。使用间充质干细胞治疗后,这些代谢物的水平发生了显著变化:研究结果表明,间充质干细胞疗法通过调节大脑胆固醇平衡和促进干细胞向神经细胞分化,具有改善AD的潜力。研究结果强调了研究胆固醇代谢物在间充质干细胞治疗中的作用的重要性,从而更深入地了解间充质干细胞对AD疗效的潜在机制。
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Adipose Tissue-Derived Mesenchymal Stem Cells Alter Metabolites of Brain Cholesterol Homeostasis in An Alzheimer's Model.

Objective: Disruption of cholesterol homeostasis in Alzheimer's disease (AD) plays a crucial role in disease pathogenesis, making it a potential therapeutic target. Mesenchymal stem cells (MSCs) show promise in treating cognitive impairment and provide a novel therapeutic approach. This study aims to investigate the effects of MSCs on specific metabolites associated with brain cholesterol homeostasis in an AD rat model.

Materials and methods: In this experimental study, animals were divided into three groups: control, AD, and AD+MSCs. AD was induced using amyloid beta (Aβ) and confirmed through the Morris water maze (MWM) behavioural test and Congo red staining. MSCs were extracted, characterised via flow cytometry, subjected to osteoblast and adipose differentiation, and injected intraventricularly. The cholesterol metabolite levels were measured using gas chromatography-mass spectrometry (GC)-MS and compared among the groups.

Results: Treatment with MSCs significantly improved memory function in the AD+MSCs group compared to the AD group and the number of beta-amyloid plaques decreased according to histological assessment. Disturbances in the brain cholesterol metabolites that included desmosterol, 7-dehydrocholesterol, 24S-hydroxycholesterol, 27-hydroxycholesterol and cholesterol were observed in the AD group compared to the control group. Treatment with MSCs resulted in significant alterations in the levels of these metabolites.

Conclusion: The findings indicate that MSC therapy has the potential to improve AD by modulating brain cholesterol homeostasis and promoting the differentiation of stem cells into nerve cells. The results emphasize the importance of investigating the role of cholesterol metabolites in the context of MSC therapy to gain deeper insights into underlying mechanisms of the therapeutic efficacy of MSCs in AD.

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来源期刊
Cell Journal
Cell Journal CELL BIOLOGY-
CiteScore
3.40
自引率
5.00%
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0
审稿时长
12 months
期刊介绍: The “Cell Journal (Yakhteh)“, formerly published as “Yakhteh Medical Journal”, is a quarterly English publication of Royan Institute. This journal focuses on topics relevant to cellular and molecular scientific areas, besides other related fields. The Cell J has been certified by Ministry of Culture and Islamic Guidance in 1999 and was accredited as a scientific and research journal by HBI (Health and Biomedical Information) Journal Accreditation Commission in 2000 which is an open access journal.
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