Cell, 13 June, 2025, DOI：https://doi.org/10.1016/j.cell.2025.05.021

Senescence-resistant human mesenchymal progenitor cells counter aging in primates

Jinghui Lei, Zijuan Xin, Ning Liu, Taixin Ning, Ying Jing, Yicheng Qiao, Zan He, Mengmeng Jiang, Yuanhan Yang, Zhiyi Zhang, Liyun Zhao, Jingyi Li, Dongliang Lv, Yupeng Yan, Hui Zhang, Lingling Xiao, Baohu Zhang, Haoyan Huang, Shuhui Sun, Fangshuo Zheng, Xiaoyu Jiang, Huifen Lu, Xueda Dong, Shasha Yue, Chencan Ma, Jichen Shuai, Zhejun Ji, Feifei Liu, Yanxia Ye, Kaowen Yan, Qinchao Hu, Gang Xu, Qian Zhao, Ruochen Wu, Yusheng Cai, Yanling Fan, Yaobin Jing, Qiaoran Wang, Pradeep Reddy, Xiaoyong Lu, Zikai Zheng, Beibei Liu, Amin Haghani, Shuai Ma, Keiichiro Suzuki, Concepcion Rodriguez Esteban, Jiayin Yang, Moshi Song, Steve Horvath, Weiqi Zhang, Wei Li, Andy Peng Xiang, Lan Zhu, Xiaobing Fu, Guoguang Zhao, Juan Carlos Izpisua Belmonte, Jing Qu, Si Wang, Guang-Hui Liu

Abstract

Aging is characterized by a deterioration of stem cell function, but the feasibility of replenishing these cells to counteract aging remains poorly defined. Our study addresses this gap by developing senescence (seno)-resistant human mesenchymal progenitor cells (SRCs), genetically fortified to enhance cellular resilience. In a 44-week trial, we intravenously delivered SRCs to aged macaques, noting a systemic reduction in aging indicators, such as cellular senescence, chronic inflammation, and tissue degeneration, without any detected adverse effects. Notably, SRC treatment enhanced brain architecture and cognitive function and alleviated the reproductive system decline. The restorative effects of SRCs are partly attributed to their exosomes, which combat cellular senescence. This study provides initial evidence that genetically modified human mesenchymal progenitors can slow primate aging, highlighting the therapeutic potential of regenerative approaches in combating age-related health decline.

文章链接：https://www.sciencedirect.com/science/article/pii/S0092867425005719?via%3Dihub