Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity

Abstract Aging impairs tendon stem/progenitor cell function and tendon homeostasis, however, effective treatments for aging‐induced tendon diseases are lacking. Exosomes are naturally derived nanoparticles that contain bioactive molecules, and therefore, have attracted great interest in tissue engineering and regenerative medicine. In this study, it is shown that young exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED‐Exos) possess abundant anti‐aging signals. These young bio‐nanoparticles can alleviate the aging phenotypes of aged tendon stem/progenitor cells (AT‐SCs) and maintain their tenogenic capacity. Mechanistically, SHED‐Exos modulate histone methylation and inhibit nuclear factor‐κB to reverse AT‐SC aging. In a naturally aging mouse model, systemic administration of SHED‐Exo bio‐nanoparticles retards tendon degeneration. Interestingly, local delivery of SHED‐Exos‐loaded microspheres confers anti‐aging phenotypes, including reduced senescent cells and decreased ectopic bone formation, thereby functionally and structurally rescuing endogenous tendon regeneration and repair capacity in aged rats. Overall, SHED‐Exos, as natural bioactive nanoparticles, have promising translational and therapeutic potential for aging‐related diseases.