Stem cell-derived extracellular vesicles as senotherapeutics

IF 12.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2024-06-22 DOI:10.1016/j.arr.2024.102391

Ekaterina Rudnitsky , Alex Braiman , Marina Wolfson , Khachik K. Muradian , Vera Gorbunova , Gadi Turgeman , Vadim E. Fraifeld

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Abstract

Cellular senescence (CS) is recognized as one of the hallmarks of aging, and an important player in a variety of age-related pathologies. Accumulation of senescent cells can promote a pro-inflammatory and pro-cancerogenic microenvironment. Among potential senotherapeutics are extracellular vesicles (EVs) (40–1000 nm), including exosomes (40–150 nm), that play an important role in cell-cell communications. Here, we review the most recent studies on the impact of EVs derived from stem cells (MSCs, ESCs, iPSCs) as well as non-stem cells of various types on CS and discuss potential mechanisms responsible for the senotherapeutic effects of EVs. The analysis revealed that (i) EVs derived from stem cells, pluripotent (ESCs, iPSCs) or multipotent (MSCs of various origin), can mitigate the cellular senescence phenotype both in vitro and in vivo; (ii) this effect is presumably senomorphic; (iii) EVs display cross-species activity, without apparent immunogenic responses. In summary, stem cell-derived EVs appear to be promising senotherapeutics, with a feasible application in humans.

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作为衰老治疗药物的干细胞衍生细胞外囊泡。

细胞衰老（CS）被认为是衰老的标志之一，也是多种与年龄有关的病症的重要因素。衰老细胞的积累会促进炎症和致癌微环境的形成。潜在的衰老治疗药物包括细胞外囊泡（EVs）（40-1000nm），包括外泌体（exosomes）（40-150nm），它们在细胞与细胞之间的交流中发挥着重要作用。在此，我们回顾了有关源自干细胞（间充质干细胞、额叶干细胞、iPSCs）以及各类非干细胞的EVs对CS影响的最新研究，并讨论了EVs发挥衰老治疗作用的潜在机制。分析表明：(i) 源自干细胞、多能细胞（ESCs、iPSCs）或多能细胞（各种来源的间充质干细胞）的EVs在体外和体内都能减轻细胞衰老表型；(ii) 这种效应可能是衰老性的；(iii) EVs显示出跨物种活性，没有明显的免疫原性反应。总之，干细胞衍生的EVs似乎是很有前景的衰老治疗药物，在人类中的应用是可行的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.