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间充质干细胞来源外泌体用于已存在的主动脉瘤的替代治疗策略

英文原题:Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell-derived exosomes.

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Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell-derived exosomes.

PubMed 2021/11/26(内容时间) Expert Opin Biol Ther Q2 · IF 4(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

MSC-ex 可能成为治疗现有 AAs 的一种新型替代治疗工具。

研究思路结论见上方概要

多项研究基于间充质干细胞来源外泌体(MSC-exs)的抗炎特性,证明了其治疗潜力。本研究旨在确定MSC-exs对动脉粥样硬化所致主动脉瘤(AAs)的治疗效果。

载脂蛋白E基因敲除小鼠经血管紧张素II诱导产生主动脉瘤后,分别注射MSC-exs或生理盐水作为对照。测量主动脉直径变化。治疗后1周,检测主动脉瘤相关蛋白表达及主动脉壁组织学。检测MSC-exs的microRNA和蛋白谱。

MSC-exs显著减轻了AA进展(生理盐水组为2.04 0.20 mm,MSC-ex组为1.34 0.13 mm,P = 0.004)。在MSC-ex组中,IL-1、TNF-和MCP-1表达降低,IGF-1和TIMP-2表达升高。MSC-ex诱导巨噬细胞向M2表型极化,并抑制主动脉壁弹性板的破坏。MSC-exs含有高水平抑制AA形成的10种microRNA,以及13种抑制炎症并促进细胞外基质合成的蛋白质。

展开英文摘要原文

Several studies demonstrated the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-exs) based on their anti-inflammatory properties. The objective was to determine the therapeutic effects of MSC-exs on aortic aneurysms (AAs) caused by atherosclerosis. RESEARCH DESIGN AND METHODS: Apolipoprotein E knockout mice with AAs induced by angiotensin II were injected with MSC-exs or saline as a control. The change in the diameter of the aorta was measured. The expression of AA-related proteins and the histology of the aortic wall were investigated at 1 week after treatment. MicroRNA and protein profiles of MSC-exs were examined.

MSC-exs significantly attenuated AA progression (2.04 0.20 mm in the saline group and 1.34 0.13 mm in the MSC-ex group, P = 0.004). In the MSC-ex group, the expression of IL-1 , TNF- and MCP-1 decreased, and expression of IGF-1 and TIMP-2 increased. MSC-ex induced the M2 phenotype in macrophages and suppressed the destruction of the elastic lamellae in the aortic wall. MSC-exs contained high levels of 10 microRNAs that inhibit AA formation and 13 proteins that inhibit inflammation and promote extracellular matrix synthesis.

MSC-ex might be a novel alternative therapeutic tool for treatment of existing AAs.

论文信息

作者
Kozakai M、Narita Y、Yamawaki-Ogata A、Fujimoto KL、Mutsuga M、Tokuda Y、Usui A
单位
Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.Japan
文献类型
非美国政府资助研究
期刊
Expert opinion on biological therapy2022 Jan
原文标识
PubMed 34823415 · DOI 10.1080/14712598.2022.2005575