Siarhei A Dabravolski, Mikhail A Popov, Aleksandra S Utkina, Gulalek A Babayeva, Anastasia O Maksaeva, Vasily N Sukhorukov, Alexander N Orekhov
{"title":"Preclinical and mechanistic perspectives on adipose-derived stem cells for atherosclerotic cardiovascular disease treatment.","authors":"Siarhei A Dabravolski, Mikhail A Popov, Aleksandra S Utkina, Gulalek A Babayeva, Anastasia O Maksaeva, Vasily N Sukhorukov, Alexander N Orekhov","doi":"10.1007/s11010-025-05285-0","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4647-4670"},"PeriodicalIF":3.7000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05285-0","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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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