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

  • Acta Pharm Sin B. 2024 Mar;14(3):1166-1186. doi: 10.1016/j.apsb.2023.12.009.
Shanshan Rao  1  2 ,  Zehui He  1  2 ,  Zun Wang  1  2  3 ,  Hao Yin  1  2 ,  Xiongke Hu  1  2  4 ,  Yijuan Tan  1  2 ,  Tengfei Wan  1  2 ,  Hao Zhu  1  2 ,  Yi Luo  1  2 ,  Xin Wang  1  2 ,  Hongming Li  1  2 ,  Zhenxing Wang  1  2 ,  Xinyue Hu  5 ,  Chungu Hong  1  2 ,  Yiyi Wang  1  2 ,  Mingjie Luo  3  6 ,  Wei Du  1  7 ,  Yuxuan Qian  1  2 ,  Siyuan Tang  3 ,  Hui Xie  1  2  8 ,  Chunyuan Chen  1  2
Affiliations
  • 1. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 2. Hunan Key Laboratory of Angmedicine, Changsha 410008, China.
  • 3. Xiangya School of Nursing, Central South University, Changsha 410013, China.
  • 4. Department of Pediatric Orthopedics, Hunan Children's Hospital, University of South China, Changsha 410007, China.
  • 5. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 6. School of Nursing, Xinjiang Medical University, Urumqi, Xinjiang 830000, China.
  • 7. Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 8. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
PMID: 38487008 DOI: 10.1016/j.apsb.2023.12.009
Abstract

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.

Keywords
Anti-aging; Cellular senescence; Extracellular vesicles; Natural aging mice; PLAU; Senescence-accelerated mice; TIMP1; Urine-derived stem cells.
Products