Effects of Human Apical Papilla Cell Senescence on Repair-related Functions in Regenerative Endodontics

INTRODUCTION: Senescence of human apical papilla cells (hAPCs) may impair their functional properties relevant to regenerative endodontic therapy. However, its impact on key cellular functions remains unclear. This study evaluated the effects of senescence on mitochondrial activity, morphology, functional behavior, and immunoinflammatory response of hAPCs. METHODS: hAPCs were allocated to non-senescent or senescent groups and stimulated with control medium, lipopolysaccharide (LPS), or LPS plus interferon-gamma. Senescence was confirmed by SA-β-Gal staining and p53 expression. Mitochondrial activity, morphology, migration, proliferation, and cytokine gene expression (tumor necrosis factor alpha, interleukin-6, interleukin-10, TGF-β) were assessed. RESULTS: Senescence induction increased SA-β-Gal activity and p53 expression. Metabolic activity was preserved under inflammatory conditions; however, senescent hAPCs showed enlarged morphology and reduced cellular extensions. Migration and proliferation were significantly impaired. Interleukin-6 expression increased and TGF-β decreased, while tumor necrosis factor alpha remained unchanged. Interleukin-10 increased only under LPS stimulation but did not compensate for the overall proinflammatory profile. CONCLUSIONS: Senescence compromises key functional properties of hAPCs and disrupts their immunoinflammatory profile, potentially affecting biological processes essential for regenerative endodontic therapy.