Inflammation Dynamics Modulate Periodontal Stem Cell Fate and Function

Abstract

The periodontium hosts diverse populations of mesenchymal stem and progenitor cells that are essential for maintaining homeostasis and driving regeneration. These include cells derived from the periodontal ligament, gingiva, and apical papilla. In health and disease, the fate and function of these stem cell populations are shaped by their microenvironment, particularly by inflammatory signals and their resolution. Chronic inflammation, such as that observed in periodontitis, disrupts the regenerative capabilities, impairing stem cell function and biasing differentiation pathways. Inflammation resolution is an active, instructive process that can restore stem cell plasticity and re-establish regenerative potential. Specialized pro-resolving lipid mediators and immune-regulatory cell types play a central role in this reprogramming. We explore how inflammation and its resolution actively shape the behavior of multiple stem cell compartments in the periodontium, highlight the emerging role of spatially organized immunoregulation, and discuss how these insights may be leveraged to develop regenerative therapies for oral and mucosal tissues. We focused on how inflammatory and resolution signals modulate osteogenic programs in periodontal MSCs and contrast these responses with those in bone marrow–derived MSCs, highlighting source-dependent differences in inflammatory susceptibility and regenerative potential.