Orofacial pathologies and engineering

Project conducted by C Chaussain, C Bardet, S. Vital and A Poliard

Tissue engineering aims at restoring the functions of an injured tissue or organ by the application of in vitro cultured cells contained within a scaffold.  Our team has developed an expertise in the field of tooth biotherapy using peptides derived from the ECM or pulp stem cells. Different mesenchymal stem cell populations, called dental pulp stem cells (DPSC), have been described in the human pulp suggesting the existence, as in the bone marrow, of a hierarchy of progenitors. Our aim is to demonstrate the feasibility of bioengineering for the injured dental pulp based on the use of progenitor/stem cells contained in the healthy dental pulp. Healthy pulp can easily be collected from shedding deciduous teeth, or following extraction of deciduous teeth, premolars or third molars performed for orthodontic treatment. We assume that the tooth is a valuable source of mesenchymal stem cells to exploit for regenerative dentistry. In addition, thanks to their multi-lineage differentiation potential, the use of these cells may also be possible for the regeneration of the craniofacial bones. In collaboration with S Germain’s lab at the Collège de France we are studying proangiogenic properties of pulp cells and developing with the lab Inserm 1148 at Bichat Hospital innovative imaging techniques to follow-up the fate implanted cell. For severe lesions leading to tooth loss, the possibility to create a Biodent is explored. In this sense, we are looking for sources of stem cells with an odontogenic potential, the use of dental embryonic tissues being excluded in humans for obvious ethical reasons. Our laboratory is labeled DIM Biothérapie (www.dim-biotherapies.com) and granted by the French Research Agency ANR (PulpCell 2014-2018), the FRM (we are labeled Team Tissue engineering), the Fondation des Gueules cassées.

As dentin and tooth cement, unlike bone, are neither remodeled nor involved in calcium and phosphorus metabolism, they are interesting tissues to study to identify pathological peptides in the context of genetic diseases affecting both bone and tooth. By analyzing extracts from dentin of patients with familial rickets (XLH with PHEX gene mutation), we identified a pathological peptide derived from the cleavage of MEPE and containing the acidic domain ASARM. This peptide, identified for the first time in human tissue mineralization, has proved a potent inhibitor of mineralization, highly resistant to proteases. We are working on neutralizing this peptide for a therapeutic target in mouse models of the disease. Other genetic diseases are being studied and we have recently unraveled a direct association between CLAUDIN16 mutations in patients with Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis and amelogenesis imperfecta. The laboratory is affiliated with the national reference Centre for rare diseases of the metabolism of phosphorus and calcium (sites.google.com/site/cdrpariscalciumphosphore; filière OSCAR) and this project is supported by IDEX grant (collaboration with INSERM team of Prof A Berdal), the Foundation of rare diseases and the association of patients with hypophosphatemic resistant rickets- (http://www.rvrh.fr/).