Brito Karynne de Nazaré Lins de, Trentin Andréa Gonçalves
Department of Cell Biology, Embryology, and Genetics, Federal University of Santa Catarina, Florianópolis, Brazil; Faculty of Medicine, Altamira Campus, Federal University of Pará, Altamira, Brazil.
Department of Cell Biology, Embryology, and Genetics, Federal University of Santa Catarina, Florianópolis, Brazil; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil.
Cytotherapy. 2025 Apr;27(4):422-437. doi: 10.1016/j.jcyt.2024.11.014. Epub 2024 Nov 22.
Cellular senescence is intricately linked with numerous changes observed in the aging process, including the depletion of the stem cell pool and the decline in tissue and organ functions. Over the past three decades, efforts to halt and reverse aging have intensified, bringing rejuvenation closer to reality. Current strategies involve treatments using stem cells or their derivatives, such as the secretome. This article aims to highlight key points and evaluate the utilization of secretome derived from mesenchymal stromal cells (MSCs) as an antisenescent approach. Employing a quasi-systematic research approach, the authors conducted a comprehensive analysis based on a search algorithm targeting the in vitro effects of MSC-derived secretome on rescuing cells from a senescent state. Reviewing 39 articles out of 687 hits retrieved from PubMed and Scopus without a time limit, the authors synthesized information and identified common types of MSC-tissue sources utilized (including bone marrow-MSCs, umbilical cord-MSCs, iPSC-derived MSCs, adipose tissue-MSCs, dental pulp-MSCs, amniotic membrane-MSCs, placenta-MSCs, gingival-MSCs, urine-MSCs, and commercially available MSC lineages) from both human and other species (such as mice and rats). The authors also examined the forms of secretome tested (including conditioned media and extracellular vesicles), the cell types treated (MSCs or other cell types), methods/biomarkers of monitoring senescence/rejuvenation, and the mechanisms involved. Ultimately, this review underscores the proof-of-principle of the beneficial effects of MSC-derived secretome in reversing cellular senescence across various cell types. Such insights might aid the scientific community in designing improved in vitro and in vivo assays for future research and clinical validation of this promising cell-free therapy.
细胞衰老与衰老过程中观察到的众多变化密切相关，包括干细胞池的耗竭以及组织和器官功能的衰退。在过去三十年中，阻止和逆转衰老的努力不断加强，使返老还童更接近现实。当前的策略包括使用干细胞或其衍生物（如分泌组）进行治疗。本文旨在突出关键点，并评估源自间充质基质细胞（MSC）的分泌组作为一种抗衰老方法的应用。作者采用准系统研究方法，基于一种搜索算法对MSC分泌组在体外将细胞从衰老状态中拯救出来的作用进行了全面分析。作者在没有时间限制的情况下，对从PubMed和Scopus检索到的687条记录中的39篇文章进行了综述，综合信息并确定了所使用的常见类型的MSC组织来源（包括骨髓MSC、脐带MSC、诱导多能干细胞衍生的MSC、脂肪组织MSC、牙髓MSC、羊膜MSC、胎盘MSC、牙龈MSC、尿液MSC和市售的MSC谱系），这些来源来自人类和其他物种（如小鼠和大鼠）。作者还研究了所测试的分泌组形式（包括条件培养基和细胞外囊泡）、所处理的细胞类型（MSC或其他细胞类型）、监测衰老/年轻化的方法/生物标志物以及涉及的机制。最终，本综述强调了MSC分泌组在逆转各种细胞类型的细胞衰老方面有益作用的原理证明。这些见解可能有助于科学界设计改进的体外和体内试验，以便对这种有前景的无细胞疗法进行未来的研究和临床验证。
