Acta Pharmaceutica Sinica B (Mar 2024)
Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1
- Shanshan Rao,
- Zehui He,
- Zun Wang,
- Hao Yin,
- Xiongke Hu,
- Yijuan Tan,
- Tengfei Wan,
- Hao Zhu,
- Yi Luo,
- Xin Wang,
- Hongming Li,
- Zhenxing Wang,
- Xinyue Hu,
- Chungu Hong,
- Yiyi Wang,
- Mingjie Luo,
- Wei Du,
- Yuxuan Qian,
- Siyuan Tang,
- Hui Xie,
- Chunyuan Chen
Affiliations
- Shanshan Rao
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Zehui He
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Zun Wang
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China; Xiangya School of Nursing, Central South University, Changsha 410013, China
- Hao Yin
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Xiongke Hu
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China; Department of Pediatric Orthopedics, Hunan Children's Hospital, University of South China, Changsha 410007, China
- Yijuan Tan
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Tengfei Wan
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Hao Zhu
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Yi Luo
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Xin Wang
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Hongming Li
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Zhenxing Wang
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Xinyue Hu
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Chungu Hong
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Yiyi Wang
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Mingjie Luo
- Xiangya School of Nursing, Central South University, Changsha 410013, China; School of Nursing, Xinjiang Medical University, Urumqi, Xinjiang 830000, China
- Wei Du
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha 410008, China
- Yuxuan Qian
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China
- Siyuan Tang
- Xiangya School of Nursing, Central South University, Changsha 410013, China; Corresponding authors.
- Hui Xie
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Corresponding authors.
- Chunyuan Chen
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Angmedicine, Changsha 410008, China; Corresponding authors.
- Journal volume & issue
-
Vol. 14,
no. 3
pp. 1166 – 1186
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.
