The developmental lineage origins of dental stem cells and their locations are not known. This is largely because most studies have utilised non-specific protein markers with cultures of human cells. Previous studies have however implied highly vascularised sites as potential stem cell niches, and perivascular / pericyte associated markers were among those found to be present on dental stem cell populations. The aim of this study is to use a mouse genetics approach to determine if pericytes are the source of dental stem cells.
Methods:
We used a transgenic mouse line expressing nuclear LacZ in pericytes to trace the distribution and molecular marker expression profile of these cells during tooth formation. In addition, tooth damage was generated to understand the response and involvement of pericytes to injury.
Results:
From bell stage onwards, LacZ-positive pericytes start to appear associated with blood vessels close to the tooth germ and also inside the dental papilla mesenchyme. Pericyte markers such as alpha smooth muscle actin (αSMA) and neuro-glial proteoglycan 2 (NG2) as well as mesencyme stem cells marker such as low-affinity nerve growth factor receptor (p75NGFR) were found co-expressed with some of the LacZ positive pericytes. Following injury to 5-day old pericyte LacZ mice teeth, pericytes were accumulated in the damaged area. Phosphohistone 3 staining showed some of these pericytes were undergoing cell proliferation.
Conclusion:
The results imply that single pericytes, not associated with vessels are found in the mesenchyme of developing teeth. In response to damage of the pulp and odontoblasts, these pericytes proliferate. Pericytes are thus closely associated with the niche created following damage. Experiments to determine if these pericytes differentiate into odontoblasts in the niche are ongoing.