Project R-16449

Epithelial cell rests of Malassez: the one percent of the periodontium? Mapping functional heterogeneity as 'para-neuroendocrine' and metabolic stem cell signaling hubs (Research)

Across the globe, severe periodontal disease affects billions, resulting in destruction of toothsupportive structures such as periodontal ligament (PDL) and eventually tooth loss. Epithelial cell rests of Malassez (ERM) are enigmatic cell clusters dispersed throughout developing and established PDL. Over the years, it has become clear that ERM have their hand on almost all processes in the PDL: painting a complex picture of ERM as central signaling conductors capable of integrating and relaying diverse stimuli (e.g. associated with bone remodeling, inflammation, immune reaction, and tissue damage) locally ('para-') and distally ('neuroendocrine'). However, we do not have clear grasp of ERM's functional diversity as 'para-neuroendocrine' (stem cell) signaling hubs and the secreted factors employed. We hypothesize that ERM consist of different functional subtypes adapted to perform specific roles. Secondly, we propose that ERM's signaling and metabolic properties are dynamic, and transform during development. By combining our established expertise in dental stem cells, organoid modeling and single-cell transcriptomics with state-of-the-art multiplexed spatial omics, we propose to bridge this gap and bring the ERM into the light. Together, by unraveling key periodontal signaling axes, this project will bring us one step closer to developing innovative, bioinspired treatments for the billions suffering from severe periodontal disease and tooth loss.

01 January 2026 - 31 December 2028