Human Atlas of Tooth Decay Progression: Identification of Cellular Mechanisms Driving the Switch from Dental Pulp Repair Toward Irreversible Pulpitis

Dental pulp responses to dental decay, the most prevalent chronic disease worldwide, involve remodeling processes comparable to those observed in other human diseases. By combining volumetric imaging and single-cell analysis at various stages of the disease in human samples, the natural history of how dental pulp responds to decay is uncovered. During the early phases, an arterialization of capillary networks and a progressive outward remodeling of larger vessels are observed. Additionally, neurogenesis of nerve endings and the reprogramming of perivascular progenitor cells into fibroblasts, initiating the physiological reparative response of the stromal tissue, is identified. Vascular and nerve regression, along with a shift in immune response and dental pulp fibrosis, contribute to irreversible pulpitis. These findings establish a foundation for a more comprehensive understanding of how dental tissues respond to injury, thereby prompting a paradigm shift in patient management strategies. Furthermore, this study underscores the potential of the human tooth as a valuable model for investigating other systemic diseases and evaluating treatment responses.