Abstract
The human dentition is a typical diphyodont mammalian system with tooth replacement of most positions. However, after dental replacement and sequential molar development, the dental lamina undergoes apoptosis and fragments, leaving scattered epithelial units (dental lamina rests; DLRs). DLRs in adult humans are considered inactive epithelia, thought to possess limited capacity for further regeneration. However, we show that these tissues contain a small proportion of proliferating cells (assessed by both Ki67 and PCNA) but also express a number of common dental stem cell markers (Sox2, Bmi1, β-catenin and PH3) similar to that observed in many vertebrates that actively, and continuously regenerate their dentition. We compared these human tissues with the dental lamina of sharks that regenerate their dentition throughout life, providing evidence that human tissues have the capacity for further and undocumented regeneration. We also assessed cases of human ameloblastoma to characterise further the proliferative signature of dental lamina rests. Ameloblastomas are assumed to derive from aberrant lamina rests that undergo changes, which are not well understood, to form a benign tumour. We suggest that dental lamina rests can offer a potential source of important dental stem cells for future dental regenerative therapy. The combined developmental genetic data from the shark dental lamina and ameloblastoma may lead to the development of novel methods to utilise these rested populations of adult lamina stem cells for controlled tooth replacement in humans.
Highlights
The human dentition is a typical diphyodont mammalian system with tooth replacement of most positions
These dental lamina rests (DLRs) are commonly found within the dental follicle (DF) of unerupted teeth and in the connective tissues which comprise the wall of the dentigerous cyst (DC) of the jaws
In order to explore the regenerative potential of DLRs, we assessed a cohort of dental follicles (DF) and dentigerous cysts (DC) for DLR content
Summary
The human dentition is a typical diphyodont mammalian system with tooth replacement of most positions. We aimed to compare these epithelial remnants (DLRs) with epithelia associated with both human ameloblastoma, and a continuously active dental lamina present in the shark (Scyliorhinus canicula) necessary for lifelong tooth regeneration[2,3] This comparison is significant to recognise the common stem-like factors within these tissues that may indicate a retained capacity for regeneration in adult human DLRs. Recent data suggests that the shark dental lamina actively and rapidly produces teeth in a conveyor belt-like process that (i) is governed by a highly conserved set of core genes shared from sharks to mammals[3] and (ii) fed by populations of progenitor cells for continuous production[2]. We hypothesise that human DLRs, common in adult oral tissues, are a potential source of stem cells (progenitors) fated for dental differentiation and could be utilised for novel tooth regeneration in humans after tooth loss
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