Pang, YWY; (2015) Functional Characteristics of Dental Pulp Mesenchymal Stem Cells. Doctoral thesis , UCL (University College London).

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Abstract

Mesenchymal stem cells (MSCs) in many adult tissues provide cell sources to sustain tissue growth and/or repair in vivo, yet MSCs are mainly studied based on their in vitro characteristics. One emerging population of such MSCs are from dental pulp mesenchymal tissue, termed dental pulp stem cells (DPSCs). For instance, the continuously growing rodent incisor model has recently provided the first in vivo evidence that the in vivo identities of MSCs are of multiple origins including from perivascular niches. However, little is known about the molecular mechanisms underlying MSC response to injury in vivo, including that in the context of tooth repair. We therefore compared processes involved in recruiting stem cells during injury repair, particularly cell migration of pulp cells isolated from distinct anatomical locations. We found pulp cells from the region containing putative stem cells showed the highest migration capacity and their migration ability could be stimulated by activating Wnt activity in vitro. Furthermore, following in vivo tooth injury on transgenic mice, Wnt/β-catenin was also found up-regulated close to the injury site, possibly regulating injury repair via promoting perivascular-associated stem cell accumulation in close proximity to the injury site. In addition, analysis of a novel injury experimental model- the incisor tip, that undergoes constant attrition/repair through natural feeding, confirmed that this rapid incisal tip repair is also facilitated by perivascular stem cells, similar to other experimental injury models, but at a far more striking level. Thus, future work will utilise this novel model to investigate regulatory mechanisms including Wnt signalling in mediating mesenchymal tissue repair. Taken together, we demonstrated that the Wnt pathway may play a crucial role in regulating MSCs during incisor injury repair in vitro and in vivo. Also, the naturally existing “incisal tip niche” is potentially a unique model for new insights into mesenchymal tissue repair in vivo.

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