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Stem cells are capable of renewing themselves through cell division and have the remarkable ability to differentiate into many different types of cells. They therefore have the potential to become a central tool in regenerative medicine. During the last decade, advances in tissue engineering and stem cell-based tooth regeneration have provided realistic and attractive means of replacing lost or damaged teeth. Investigation of embryonic and adult (tissue) stem cells as potential cell sources for tooth regeneration has led to many promising results. However, technical and ethical issues have hindered the availability of these cells for clinical application. The recent discovery of induced pluripotent stem (iPS) cells has provided the possibility to revolutionize the field of regenerative medicine (dentistry) by offering the option of autologous transplantation. In this article, we review the current progress in the field of stem cell-based tooth regeneration and discuss the possibility of using iPS cells for this purpose.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disorder due to a mutation of Eda gene and mainly characterized by an absence or deficient function of hair, teeth and sweat glands, and craniofacial dysmorphologies. Although the tooth abnormalities in Tabby mutant mice -the murine model of XLHED- have been extensively studied, the characterization of the craniofacial complex, and especially the mandibular morphology has received less attention. From 3D microCT reconstructions of the left mandible, the mandibular outline, in lateral view, was quantified using 2D elliptical Fourier analysis. Comparisons between Tabby specimens and their wild type controls were carried out showing significant shape differences between the mouse strains enabling a clear distinction between hemizygous Tabby specimens and the other mouse groups (WT and heterozygous EdaTa/+ specimens). Morphological differences associated to HED correspond not only to global mandibular features (restrained development of that bone along dorsoventral axis), but subtle aspects (marked backward projection of the coronoid process and narrower neck of the mandibular condyle), providing, for the first time, evidences of a predominant effect of the Ta mutation on the mandibular morphology. Such result parallels the well described abnormalities of jugal tooth row and skeletal defects in Ta mice, underlining the role of EDA-A in the reciprocal epithelial-mesenchymal interactions that are of critical importance in the normal dental and craniofacial development.

The implantation of cultured re-associations between embryonic dental mesenchymal cells and epithelial cells from mouse molars at ED14 allowed making full teeth with crown, root, periodontal ligament fibers and bone. Although representing valuable tools to set up methodologies embryonic cells are not easily available. This work thus aimed to replace the embryonic cells by dental mesenchymal cell lines or cultured expanded embryonic cells, and to test their ability to mediate tooth development in vitro when re-associated with a competent dental epithelium. Histology, immunostaining and RT-PCR allowed getting complementary sets of results. Two different immortalized cell lines from ED18 dental mesenchyme failed in mediating tooth formation. The potentialities of embryonic dental mesenchymal cells decreased from ED14 to ED16 and were lost at ED18. This is likely related to a change in the mesenchymal cell phenotype and/or populations during development. Attempts to cultivate ED14 or ED16 embryonic dental mesenchymal cells prior to re-association led to the loss of their ability to support tooth development. This was accompanied by a down-regulation of Fgf3 transcription. Supplementation of the culture medium with FGF2 allowed restoring Fgf3 expression, but not the ability of mesenchymal cells to engage in tooth formation. Altogether, these observations suggest that a competent cell population exists in the dental mesenchyme at ED14, progressively decreases during development, and cannot as such be maintained in vitro. This study evidenced the need for specific conditions to maintain the ability of dental mesenchymal cells to initiate whole tooth formation, when re-associated with an odontogenic epithelium. Efforts to improve the culture conditions will have to be combined with attempts to characterize the competent cells within the dental mesenchyme.