Wong Pooi-Fong, Dharmani Murugan, Ramasamy Thamil Selvee
Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Wilayah Persekutuan Kuala Lumpur, Malaysia.
Stem Cell Biology Laboratory, Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603 Wilayah Persekutuan Kuala Lumpur, Malaysia.
Drug Discov Today. 2023 Jan;28(1):103424. doi: 10.1016/j.drudis.2022.103424. Epub 2022 Nov 1.
Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.
间充质干细胞（MSCs）易发生复制性衰老和衰老相关的功能衰退，这阻碍了它们在再生医学中的应用。衰老疗法是通过溶衰老和衰老形态功能靶向细胞衰老的药物，分别诱导凋亡和抑制由衰老相关分泌表型（SASP）引起的慢性炎症。因此，衰老疗法可以延缓与衰老相关的退化。它们还可用于在体外扩增或生物加工用于移植的过程中消除衰老的间充质干细胞。在这篇综述中，我们讨论了衰老疗法在间充质干细胞衰老、年轻化和移植中的作用，并列举了一些体外测试化合物的例子。还讨论了衰老疗法在基于细胞的治疗中的临床应用前景、挑战和未来方向。
