Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

• Published in: Acta pharmaceutica Sinica. B 2024-03, Vol.14 (3), p.1166-1186
• Main Authors: Rao, Shanshan, He, Zehui, Wang, Zun, Yin, Hao, Hu, Xiongke, Tan, Yijuan, Wan, Tengfei, Zhu, Hao, Luo, Yi, Wang, Xin, Li, Hongming, Wang, Zhenxing, Hu, Xinyue, Hong, Chungu, Wang, Yiyi, Luo, Mingjie, Du, Wei, Qian, Yuxuan, Tang, Siyuan, Xie, Hui, Chen, Chunyuan
• Format: Article
• Language: English
• Subjects: Anti-aging; Cellular senescence; Extracellular vesicles; Natural aging mice; Original; PLAU; Senescence-accelerated mice; TIMP1; Urine-derived stem cells
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2023.12.009

Aging increases the risks of various diseases and the vulnerability to death. Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases. This study demonstrates that extracellular vesicles from human urine-derived stem cells (USC-EVs) efficiently inhibit cellular senescence in vitro and in vivo. The intravenous injection of USC-EVs improves cognitive function, increases physical fitness and bone quality, and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging mice. The anti-aging effects of USC-EVs are not obviously affected by the USC donors’ ages, genders, or health status. Proteomic analysis reveals that USC-EVs are enriched with plasminogen activator urokinase (PLAU) and tissue inhibitor of metalloproteinases 1 (TIMP1). These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases, cyclin-dependent kinase inhibitor 2A (P16INK4a), and cyclin-dependent kinase inhibitor 1A (P21cip1). These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins. Aged-mice treated with USC-EVs improved the structure and function of various organs by transferring PLAU and TIMP1 proteins, rejuvenating the old organ towards a more “youthful” state. [Display omitted]