鹿茸芽基祖细胞来源的细胞外囊泡可逆转小鼠和猕猴的骨质流失并减轻衰老相关表型。
Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques.
作者信息
Hao Yiming, Yu Beibei, Qin Mingze, Qin Tao, Wang Jianhong, Wei Yitao, Zhao Chengxiang, Xing Yaowen, Yuan Yuan, Xue Tingfeng, Xue Borui, Zhang Yali, Huang Hongdi, Yu Xiaomei, Ji Yunchao, Qiu Minghao, Zhou Yufang, Xia Bing, Ma Teng, Li Shengyou, Wu Haining, Gao Xue, Yang Yujie, Guo Lingli, Zhang Yongfeng, Wang Zhenguo, Sun Huiling, Gao Xueli, Huang Zujian, Lv Longbao, Wu Dongdong, Li Zhipeng, Yao Yonggang, Wang Wen, Luo Zhuojing, Qiu Qiang, Huang Jinghui
机构信息
Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Neurosurgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
出版信息
Nat Aging. 2025 Jul 14. doi: 10.1038/s43587-025-00918-x.
Antler blastema progenitor cells (ABPCs) are a distinct population of skeletal mesenchymal stem cells found in regenerating deer antlers, with strong stemness and renewal capacity in vitro. Stem cell-derived extracellular vesicles (EVs) are emerging as potential therapeutic candidates that can mediate donor cells' beneficial effects. Here, we tested the effects of ABPC-derived EVs (EVs) on aging in mice and rhesus macaques (Macaca mulatta). We identified a variety of unique factors in EVs and showed that in vitro, EVs attenuated phenotypes of senescence in bone marrow stem cells. In aged mice and macaques, EVs substantially increased femoral bone mineral density. Further, intravenous EVs improved physical performance, enhanced cognitive function and reduced systemic inflammation in aged mice, while reversing epigenetic age by over 3 months. In macaques, EV treatment was also neuroprotective, reduced inflammation, improved locomotor function and reduced epigenetic age by over 2 years. Our findings position ABPCs as an emerging and practical source of EVs with translational value for healthy aging interventions.
鹿茸芽基祖细胞(ABPCs)是在再生鹿角中发现的一种独特的骨骼间充质干细胞群体,在体外具有强大的干性和更新能力。干细胞衍生的细胞外囊泡(EVs)正成为潜在的治疗候选物,能够介导供体细胞的有益作用。在此,我们测试了ABPC衍生的EVs对小鼠和恒河猴衰老的影响。我们在EVs中鉴定出多种独特因子,并表明在体外,EVs减轻了骨髓干细胞的衰老表型。在老年小鼠和恒河猴中,EVs显著增加了股骨骨矿物质密度。此外,静脉注射EVs改善了老年小鼠的身体机能,增强了认知功能,减轻了全身炎症,同时使表观遗传年龄逆转超过3个月。在恒河猴中,EV治疗还具有神经保护作用,减轻了炎症,改善了运动功能,并使表观遗传年龄逆转超过2年。我们的研究结果将ABPCs定位为一种新兴且实用的EVs来源,对健康衰老干预具有转化价值。