抗衰老的人间充质祖细胞可对抗灵长类动物的衰老。

Senescence-resistant human mesenchymal progenitor cells counter aging in primates.

作者信息

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

机构信息

Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital Capital Medical University, Beijing 100053, China; State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.

出版信息

Cell. 2025 Jun 13. doi: 10.1016/j.cell.2025.05.021.

DOI:10.1016/j.cell.2025.05.021

PMID:40516525

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.

摘要

衰老的特征是干细胞功能衰退，但补充这些细胞以对抗衰老的可行性仍不明确。我们的研究通过开发抗衰老的人间充质祖细胞（SRCs）来填补这一空白，这些细胞经过基因强化以增强细胞韧性。在一项为期44周的试验中，我们将SRCs静脉注射给老年猕猴，发现衰老指标如细胞衰老、慢性炎症和组织退化出现全身性减少，且未检测到任何不良反应。值得注意的是，SRC治疗增强了脑结构和认知功能，并缓解了生殖系统衰退。SRCs的恢复作用部分归因于它们的外泌体，这些外泌体可对抗细胞衰老。这项研究提供了初步证据，表明基因改造的人间充质祖细胞可以延缓灵长类动物衰老，凸显了再生方法在对抗与年龄相关的健康衰退方面的治疗潜力。