Harnessing Dental Pulp Stem Cells to Enhance Tissue Regeneration

Dental decay continues to be the most prevalent infectious disease in the world, affecting 80% of adults. In England and Wales, dentists place 20 million restorations due to recurrent decay each year at a cost of #173 million. Replacement of failing restorations accounts for 80% of clinical work. If untreated, infection progresses to the central pulp (nerve) of the tooth affecting general health, reducing quality of life. Dental infection is the commonest reason for lost working days and continued infection leads to dental abscess formation outside the tooth, where systemic migration of bacteria has been linked with heart and blood infections. A future ageing population will increase these problems. The dental pulp contains several populations of potential immature cells. One population is associated with the blood vessels and we have recently isolated two further immature cell populations from dental pulp of developing teeth and embryonic tissue origin. These cells are likely to play key roles in the repair process, able to mature into dental tissue (dentine) forming cells (odontoblasts) and lay down reparative tissue at the dentine-pulp boundary to regenerate lost tissue. Importantly, this reparative dentine is capable of providing a natural barrier to bacteria leaching from around a restoration. A therapeutic approach to improving longevity of dental restorations is to develop novel restorative materials so that they attract the immature cells to a site below the restoration and stimulate tissue regeneration. To develop this approach we need to understand the responses of these immature cells to their natural micro-environments and current restorative materials. We have demonstrated that existing dental materials are capable of stimulating reparative dentine formation by encouraging the release of bioactive molecules from surrounding dentine. This project aims to harness and manipulate such molecules in materials which can then be used to encourage immature cells to form reparative dentine. We will investigate the ability to incorporate such molecules into novel and existing materials and test their ability to stimulate repair in tissue cultures. The overall objective being the development of a prototype smart ?biofilling?.

The dentine?pulp complex displays exquisite regenerative potential in response to injury. Existing methods of treatment (composite fillings, calcium hydroxide) for extensive dental caries involving deep cavitiation and pulpal exposure have a high failure rate leading to costly and painful re-treatment. A population of multipotent mesenchymal progenitor cells known as dental pulp stem cells (DPSCs) with high proliferative potential for self-renewal has been described and underpins the natural regenerative capacity of the tissue. Growth factors sequestered within the dentine matrix signals to these cells mediating the natural reparative response. Manipulating the potentialities of this population of DPSCs within the tissue is important in developing strategies to recruit such cells to sites of injury, allowing exploitation of their use in regeneration of damaged tissue and development of new clinical treatment modalities. This proposal will exploit our current understanding of how growth factors and dentine matrix mediate dental tissue regeneration by stimulating this population of DPSCs to develop biomimetic restorative materials to drive recruitment and differentiation of DPSCs in situ leaading to regeneration of dental tissue, providing a more accessible and clinically translational outcome for pre-clinical stem cell research.