Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques

Antler blastema progenitor cell (ABPC) is a novel type of skeletal stem cells with strong stemness and renewal ability. Here, we discovered that ABPC-derived extracellular vesicles (EVsABPCs) can strongly rejuvenate aging tissues in aged mice and rhesus macaques (Macaca mulattas). We identified a variety of rejuvenating signals in EVsABPCs, which exhibited a robust in vitro ability to rejuvenate senescent bone marrow stromal stem cells. In vivo, EVsABPCs increased bone mineral density in femur by 2.4-fold in mice, and 1.53-fold in rhesus macaques. Besides, intravenous EVsABPCs significantly outperformed fetal-EVsBMSCs in improving physical performance, reducing systemic inflammation and rejuvenating major tissues of aged mice, with no observed immunological side effects. Notably, EVsABPCs showed similar rejuvenating effects in old rhesus macaques as in elderly mice. These findings suggest that ABPC is a novel and practical source of EVs containing unique rejuvenating factors and has considerable translational value for anti-aging interventions, particularly rejuvenation of aging bones. Three monkeys were randomly divided into three groups, with three monkeys in each group, namely the Vehicle group (injected with PBS); EVs FBMSC group (injection of EVs FBMSC); EVs ABPC group (injection of EVs ABPC)