Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Abstract

Fibroblast activation protein-alpha (FAP alpha) is a membrane protein with dipeptidyl-peptidase and type I collagenase activity and is expressed during fetal growth. At the age of adolescence, FAP alpha expression is greatly reduced, only emerging in pathologies associated with extracellular matrix remodeling. We determined whether FAP alpha is expressed in human dental tissue involved in root maturation i.e., dental follicle and apical papilla and in dental pulp tissue. The dental follicle revealed a high concentration of FAP alpha and vimentin-positive cells within the stromal tissue. A similar observation was made in cell culture and FACS analysis confirmed these as dental follicle stem cells. Within the remnants of the Hertwigs' epithelial root sheath, we observed FAP alpha staining in the E-cadherin positive and vimentin-negative epithelial islands. FAP alpha- and vimentin-positive cells were encountered at the periphery of the islands suggesting an epithelial mesenchymal transition process. Analysis of the apical papilla revealed two novel histological regions; the periphery with dense and parallel aligned collagen type I defined as cortex fibrosa and the inner stromal tissue composed of less compacted collagen defined as medulla. FAP alpha expression was highly present within the medulla suggesting a role in extracellular matrix remodeling. Dental pulp tissue uncovered a heterogeneous FAP alpha staining but strong staining was noted within odontoblasts.In vitrostudies confirmed the presence of FAP alpha expression in stem cells of the apical papilla and dental pulp. This study identified the expression of FAP alpha expression in dental stem cells which could open new perspectives in understanding dental root maturation and odontoblast function.