Project R-15140

Epithelial cell rests of Malassez: the one percent of the periodontium? Mapping functional heterogeneity as ‘para-neuroendocrine’ stem cell signalling hubs (Research)

Across the globe, severe periodontal disease affects billions, resulting in destruction of tooth-supportive 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 (i.e. bone remodeling-, mechanical-, inflammatory-, immune- and tissue damage associated) 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. I hypothesize that ERM consist of different functional subtypes adapted to perform specific roles. By combining my developed expertise in organoid modeling and single-cell transcriptomics with state-of-the-art multiplexed spatial omics, I propose to bridge this gap and bring the ERM into the light. In addition, I will develop bioengineered ERM-containing PDL, taking advantage of my lab’s expertise in tendinogenic differentiation of PDL stem cells. Together, my project will bring us one step closer to treating the billions suffering from severe periodontal disease and tooth loss.

01 November 2024 - 31 October 2027