Sekenova Aliya, Li Yelena, Issabekova Assel, Saparov Arman, Ogay Vyacheslav
Laboratory of Stem Cells, National Center for Biotechnology, Astana 010000, Kazakhstan.
Department of Medicine, School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan.
Cells. 2023 Sep 13;12(18):2262. doi: 10.3390/cells12182262.
Atherosclerosis (AS) is an inflammatory disease involving multiple factors in its initiation and development. In recent years, the potential application of mesenchymal stem cells (MSCs) for treating AS has been investigated. This study examined the effect of TNF-α preconditioning on MSCs' therapeutic efficacy in treating AS in ApoE KO mice. TNF-α-treated MSCs were administered to high-fat diet-treated ApoE KO mice. Cytokine and serum lipid levels were measured before and after treatment. Cryosections of the atherosclerotic aorta were stained with Oil-Red-O, and the relative areas of atherosclerotic lesions were measured. The level of Tregs were increased in TNF-α-MSC-treated animals compared to the MSCs group. In addition, the systemic administration of TNF-α-MSCs to ApoE KO mice reduced the level of proinflammatory cytokines such as TNF-α and IFN-γ and increased the level of the immunosuppressive IL-10 in the blood serum. Total cholesterol and LDL levels were decreased, and HDL levels were increased in the TNF-α-MSCs group of ApoE KO mice. A histological analysis showed that TNF-α-MSCs decreased the size of the atherosclerotic lesion in the aorta of ApoE KO mice by 38%, although there was no significant difference when compared with untreated MSCs. Thus, our data demonstrate that TNF-α-MSCs are more effective at treating AS than untreated MSCs.
动脉粥样硬化（AS）是一种在其发生和发展过程中涉及多种因素的炎症性疾病。近年来，间充质干细胞（MSCs）在治疗AS方面的潜在应用受到了研究。本研究检测了肿瘤坏死因子-α（TNF-α）预处理对MSCs治疗载脂蛋白E基因敲除（ApoE KO）小鼠AS疗效的影响。将经TNF-α处理的MSCs注射到高脂饮食喂养的ApoE KO小鼠体内。在治疗前后检测细胞因子和血脂水平。用油红O对动脉粥样硬化主动脉的冰冻切片进行染色，并测量动脉粥样硬化病变的相对面积。与MSCs组相比，TNF-α-MSCs处理的动物体内调节性T细胞（Tregs）水平升高。此外，对ApoE KO小鼠全身注射TNF-α-MSCs可降低血清中TNF-α和干扰素-γ等促炎细胞因子的水平，并提高免疫抑制性白细胞介素-10的水平。ApoE KO小鼠的TNF-α-MSCs组总胆固醇和低密度脂蛋白水平降低，高密度脂蛋白水平升高。组织学分析表明，TNF-α-MSCs使ApoE KO小鼠主动脉中动脉粥样硬化病变的大小减少了38%，尽管与未处理的MSCs相比无显著差异。因此，我们的数据表明，TNF-α-MSCs在治疗AS方面比未处理的MSCs更有效。
