Stem cells in the face: tooth regeneration and beyond

Abstract

The face distinguishes one person from another. Postnatal orofacial tissues harbor rare cells that exhibit stem cell properties. Despite unmet clinical needs for reconstruction of tissues lost in congenital anomalies, infections, trauma, or tumor resection, how orofacial stem/progenitor cells contribute to tissue development, pathogenesis, and regeneration is largely obscure. This perspective article critically analyzes the current status of our understanding of orofacial stem/progenitor cells, identifies gaps in our knowledge, and highlights pathways for the development of regenerative therapies.

Figure 1

Diagrams of human and mouse orofacial tissues from which stem/progenitor cells have been studied. A: Putative epithelial stem cells reside in the developing tooth germ, oral epithelium and salivary gland. Connective tissue stem/progenitor cells (of mesenchyme/mesoderm origin) have been isolated from calvarial bone, tooth pulp, dental papilla, the periodontal ligament and marrow of alveolar bone. B: The developing rodent incisors have been the most prevalent model for studying orofacial epithelium stem cells. Rodent incisors undergo continuous growth and eruption in life. The cervical loop of the developing incisor harbors both epithelial and mesenchyme stem cells. Epithelial stem cells are known to give rise to transient amplifying cells that propagate and migrate anteriorly and differentiate intoameloblasts that produce enamel matrix. Strikingly, enamel is produced only on the labial side in rodents. In contrast, mesenchyme stem cells migrate anteriorly to differentiateinto odontoblasts that produce dentin, in addition to likely giving rise to interstitial fibroblast-like cells in dental pulp, among which very few cells are stem/progenitor cells that are typically quiescent and serve to replenish pulp cells, including upon injury or pathological insult.