脂肪来源干细胞治疗动脉粥样硬化性心血管疾病的临床前和机制研究

IF 3.7 2区 生物学 Q3 CELL BIOLOGY
Molecular and Cellular Biochemistry Pub Date : 2025-08-01 Epub Date: 2025-04-16 DOI:10.1007/s11010-025-05285-0
Siarhei A Dabravolski, Mikhail A Popov, Aleksandra S Utkina, Gulalek A Babayeva, Anastasia O Maksaeva, Vasily N Sukhorukov, Alexander N Orekhov
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引用次数: 0

摘要

脂肪源性间充质干细胞(AD-MSCs)具有免疫调节、抗炎和促血管生成的特性,是一种很有前景的心血管疾病治疗方式。本文探讨了AD-MSC治疗的现状、挑战和未来发展方向,重点关注其在动脉粥样硬化(AS)、心肌梗死(MI)和心力衰竭(HF)中的应用。临床前研究强调了AD-MSC通过巨噬细胞极化、内皮保护和血管生成等机制稳定动脉粥样硬化斑块、减少炎症和增强心肌修复的能力。基因和药理学修饰的AD-MSCs,包括过表达SIRT1、IGF-1和PD-L1或生物活性化合物的AD-MSCs,与未修饰的细胞相比,表现出优越的疗效。这些修饰提高了细胞存活率、免疫效力和修复能力,显示了定制治疗的潜力。然而,临床翻译面临着重大障碍。虽然最近的临床试验已经证实了AD-MSC治疗的安全性,但其疗效仍然不一致,需要进一步优化患者选择、给药策略和给药方法。供体的可变性,特别是伴有2型糖尿病(T2D)或肥胖等合并症的患者,会损害AD-MSC的疗效。来自AD-MSC的细胞外囊泡(EVs)的新兴研究提供了一种有前途的无细胞替代方案,在保持治疗效果的同时降低了风险。未来的观点强调需要多学科方法来克服这些限制。策略包括改进基因修饰,探索基于ev的疗法,以及整合个性化医疗和先进的诊断工具。通过解决这些挑战,AD-MSC疗法有可能彻底改变心血管疾病的治疗,提供创新的解决方案来改善患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preclinical and mechanistic perspectives on adipose-derived stem cells for atherosclerotic cardiovascular disease treatment.

Adipose-derived mesenchymal stem cells (AD-MSCs) are a promising therapeutic modality for cardiovascular diseases due to their immunomodulatory, anti-inflammatory, and pro-angiogenic properties. This manuscript explores the current status, challenges, and future directions of AD-MSC therapies, focusing on their application in atherosclerosis (AS), myocardial infarction (MI), and heart failure (HF). Preclinical studies highlight AD-MSC's ability to stabilise atherosclerotic plaques, reduce inflammation, and enhance myocardial repair through mechanisms such as macrophage polarisation, endothelial protection, and angiogenesis. Genetically and pharmacologically modified AD-MSCs, including those overexpressing SIRT1, IGF-1, and PD-L1 or primed with bioactive compounds, exhibit superior efficacy compared to unmodified cells. These modifications enhance cell survival, immunopotency, and reparative capacity, showcasing the potential for tailored therapies. However, clinical translation faces significant hurdles. While recent clinical trials have confirmed the safety of AD-MSC therapy, their efficacy remains inconsistent, necessitating further optimisation of patient selection, dosing strategies, and delivery methods. Donor variability, particularly in patients with co-morbidities like type 2 diabetes (T2D) or obesity, impairs AD-MSC efficacy. Emerging research on extracellular vesicles (EVs) derived from AD-MSC offers a promising cell-free alternative, retaining the therapeutic benefits while mitigating risks. Future perspectives emphasise the need for multidisciplinary approaches to overcome these limitations. Strategies include refining genetic modifications, exploring EV-based therapies, and integrating personalised medicine and advanced diagnostic tools. By addressing these challenges, AD-MSC therapies hold the potential to revolutionise the treatment of cardiovascular diseases, providing innovative solutions to improve patient outcomes.

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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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