Elmi Faranak, Soltanmohammadi Fatemeh, Fayeghi Tahura, Farajnia Safar, Alizadeh Effat
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Regen Ther. 2025 May 5;29:517-539. doi: 10.1016/j.reth.2025.04.014. eCollection 2025 Jun.
The efficacy of mesenchymal stem cells (MSCs) mediated regenerative therapies has been hindered by the senescence of them during long period cultures. Aged MSCs exhibit altered morphology, decreased stemmas, changed intercellular communication, and poor differentiation ability. Besides in physiological condition, upon transplantation of senescent MSCs, they are capable of activating both the innate and adaptive immune systems, playing a crucial role in preserving tissue homeostasis. Therefore, enhancing immunomodulation properties and preventing aging progress of MSCs to achieve successful future clinical applications seems necessary. This review delves into the current knowledge of the underlying cellular and molecular mechanisms that promote MSCs senescence as well as the developed approaches for reversing or preventing MSCs aging. These include pre-treatment of MSCs with various types of molecules to inhibit aging process and implementation of different types of three-dimensional culture systems. In addition, the recently developed strategies to improve immunomodulatory properties of MSCs have been discussed. By addressing the limitations of aged MSCs and augmenting their immunomodulation, these approaches offer a promising avenue for the future of cell therapy and provide valuable tools for maximizing the effectiveness of MSCs therapy in biomedical applications.
间充质干细胞（MSCs）介导的再生疗法的疗效受到其在长期培养过程中衰老的阻碍。衰老的MSCs表现出形态改变、干细胞特性降低、细胞间通讯改变以及分化能力差。除了在生理条件下，衰老的MSCs移植后能够激活先天性和适应性免疫系统，在维持组织稳态中发挥关键作用。因此，增强MSCs的免疫调节特性并防止其衰老进程以实现未来成功的临床应用似乎是必要的。这篇综述深入探讨了促进MSCs衰老的潜在细胞和分子机制的当前知识，以及已开发的逆转或防止MSCs衰老的方法。这些方法包括用各种类型的分子对MSCs进行预处理以抑制衰老过程，以及实施不同类型的三维培养系统。此外，还讨论了最近开发的改善MSCs免疫调节特性的策略。通过解决衰老MSCs的局限性并增强其免疫调节能力，这些方法为细胞治疗的未来提供了一条有前景的途径，并为在生物医学应用中最大化MSCs治疗的有效性提供了有价值的工具。
