Sustained Inflammatory Stimulation Induced Inflammatory Memory In Dpscs

During pulp inflammation, dental pulp stem cells (DPSCs) migrate to the inflammatory site, receive signals from the microenvironment, and differentiate into newly formed odontoblasts. However, the mechanisms by which DPSCs respond to repeated inflammatory stimulation remain unclear. Recent studies suggest that, beyond classical adaptive immune memory, tissue-resident stem cells within the innate immune system can develop immune memory, resulting in enhanced responses to subsequent stimuli. Whether DPSCs acquire such innate immune memory after repeated inflammatory exposure remains unknown. This study aimed to investigate whether repeated inflammatory stimulation induces inflammatory memory in DPSCs. DPSCs were cultured and repeatedly stimulated with the proinflammatory cytokine TNF-α to induce inflammatory memory. Gene expression and protein levels of inflammatory cytokine expression were assessed. Additionally, the multipotent differentiation potential of DPSCs, including odontogenic, neurogenic, and adipogenic differentiation, was evaluated to determine the impact of inflammatory memory. Repeated TNF-α stimulation induced sustained inflammatory memory in DPSCs, with significantly enhanced IL6, IL8, and IL1β expression upon re-stimulation. This memory lasted at least six days. Notably, Inflammatory memory showed non-specificity, with elevated responses even to heterologous stimuli. However, it impaired the multipotent differentiation capacity of DPSCs. These findings demonstrate that inflammatory stimulation imprints trained memory in DPSCs, altering their responses to future challenges and compromising their stem cell characteristics.