Role of Cellular Senescence On The Immune Inflammatory Response and Regenerative Capacity of Human Dental Pulp Cells - A Systematic Review

Abstract

Background: Cellular senescence is a state of irreversible growth arrest that profoundly alters tissue homeostasis through proinflammatory and degenerative signaling. In the dental pulp, senescence disrupts the balance between immune regulation and regeneration, potentially compromising the success of conservative and regenerative endodontic therapies. Understanding how senescence affects the immune-inflammatory and reparative functions of human dental pulp cells (hDPCs) is crucial for developing strategies to preserve pulp vitality and combat age-related dental degeneration.

Aim: This systematic review aimed to evaluate and synthesize existing evidence on the impact of cellular senescence on the immune-inflammatory response and regenerative potential of human dental pulp cells.

Methods: A systematic literature search was conducted across Google Scholar, PubMed, and ScienceDirect for studies published between 2000 and 2025, using combinations of keywords including “dental pulp cells,” “senescence,” “immune response,” “inflammation,” and “regeneration.” Both experimental and review studies investigating senescence in hDPCs or hDPSCs were included. Data extraction focused on cellular function, gene expression, inflammatory cytokines, and molecular pathways. The synthesis followed PRISMA guidelines, and methodological quality was assessed using the Joanna Briggs Institute (JBI) checklist.

Results: Five key studies met the inclusion criteria. Across all studies, senescent hDPCs exhibited reduced proliferation, migration, and differentiation capacity, accompanied by morphologic alterations and increased expression of proinflammatory mediators such as IL-6, IL-8, and TNF-α. Transcriptomic and molecular analyses revealed downregulation of regenerative factors like TGF-β and VEGF and activation of pathways linked to oxidative stress, NF-κB signaling, and telomere dysfunction. Visfatin was identified as a novel inducer of senescence, promoting SASP activation and inflammation. Collectively, these findings demonstrate that cellular senescence fosters a proinflammatory microenvironment, impairing the pulp’s ability to regenerate and repair under stress.

Conclusion: Cellular senescence critically alters the immune-inflammatory and regenerative balance of dental pulp cells, contributing to tissue aging and reduced reparative potential. Targeting senescence-associated pathways—such as visfatin inhibition, AMPK modulation, or SASP suppression—represents a promising therapeutic avenue for maintaining pulp vitality and improving outcomes in regenerative dentistry.