Preventing MSC aging and enhancing immunomodulation: Novel strategies for cell-based therapies

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.