Stem cells and tooth germs: the end of plastic?Photo

Today’s routine dentistry would entail a prosthodontist ‘filling’ a gap in the mouth created by a missing tooth, using prosthetic appliances. Depending on the circumstance, a patient has several options to choose from, for example dentures, bridges and implants. However the implementation of this appliances would sets the patient into a requirement of continuous prosthetic intervention for the rest of their life, as each appliance has an end date, beyond which it will no longer function successfully.

As science evolves, so does our knowledge in dentistry. Stem cells “are characterized as undifferentiated cells, able to self-renew with a high proliferative capacity” [1]. Tissue engineering using stem cells and tooth germs has developed interest in dentistry, as it holds the potential “to accommodate mammalian cells and guide their growth” [2] into a whole tooth. Implants of natural whole teeth with supporting periodontal ligament would not only result in treatment being successful, it would be vastly more comfortable and prevent any personal problems regarding issues with self-appearance from developing. However, is this theory limited to fantasy, or can we truly harness tissue engineering to our advantage?

Although experiments has been carried out in producing whole natural teeth, some being successful, it is safe to say that research is in its preliminary stages. Going through all of the research papers referenced in this poster, the earliest paper to have been published regarding tooth generation was in 2002. Even if whole teeth were successfully produced, the experiments were being carried out on mice. This suggests that the results may differ when the techniques are applied to human patients.

In the experiment where a whole tooth was created, the periodontal ligament stem cells that were used were from extracted human wisdom teeth [3]. Where would the periodontal stem cells be utilised from if the patient had healthy wisdom teeth, or didn’t require extraction?From the research carried out, it is apparent that a successful combination of epithelial cells and mesenchymal cells, which would be stimulated by one

Introduction

Discussion and Conclusions

Results

SCHOOL OF DENTISTRYLiverpool, L69 3GN, UK. email: email address

[1] Kern, S., Eichler, H., Stoeve, J., Kluter, H., Bieback, K. (2006) 'Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose TissueS', Stem Cells, 24(5), pp. 1294-1301 [Online]. Available at: http://onlinelibrary.wiley.com.liverpool.idm.oclc.org/doi/10.1634/stemcells.2005-0342/full (Accessed: 15th January 2017).[2] Yang, S., Leong, K.F., Du,Z., Chua, C.K. (2002) 'The Design of Scaffold for Use in Tissue Engineering. Part II. Rapid Prototyping Techniques', Tissue Engineering, 8(1), pp. 1-11 [Online]. Available at: http://online.liebertpub.com.liverpool.idm.oclc.org/doi/pdf/10.1089/107632702753503009 (Accessed: 14th January 2017).[3] Nakahara, T. (2011) 'Potential feasibility of dental stem cells for regenerative therapies: stem cell transplantation and whole-tooth engineering', Odontology, 99(), pp. 105-111 [Online]. Available at: http://link.springer.com.liverpool.idm.oclc.org/article/10.1007/s10266-011-0037-y (Accessed: 9th January 2017).[4] Volponi, A.A., Kawasaki, M., Sharpe, P.T. (2013) 'Adult Human Gingival Epithelial Cells as a Source for Whole-tooth Bioengineering', J Dent Res, 92(4), pp. 329-334 [Online]. Available at: http://journals.sagepub.com/doi/full/10.1177/0022034513481041 (Accessed: 9th January 2017).[5] Volponi, A.A., Pang, Y., Sharpe, P.T. (2010) 'Stem cell-based biological tooth repair and regeneration', Trends in Cell Biology, 20(12), pp. 715-722 [Online]. Available at: http://www.sciencedirect.com.liverpool.idm.oclc.org/science/article/pii/S0962892410002102 (Accessed: 9th January 2017).[6] Egusa, H., Sonoyama, W., Nishimura, M., Atsuta, I., Akiyama,K. (2012) 'Stem cells in dentistry – Part I: Stem cell sources', Journal of Prosthodontic Research, 56(), pp. 151-165 [Online]. Available at: http://www.sciencedirect.com/science/article/pii/S1883195812000606 (Accessed: 9th January 2017).[7] NCBI (2017) DSPP dentin sialophosphoprotein [ Homo sapiens (human) ], Available at: https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1834 (Accessed: 23rd January 2017).[8] Page, R.C., Kornman, K.S. (2000) 'The pathogenesis of human periodontitis:an introduction', Periodontology 2000, 14(1), pp. 9-11 [Online]. Available at: http://onlinelibrary.wiley.com.liverpool.idm.oclc.org/doi/10.1111/j.1600-0757.1997.tb00189.x/full (Accessed: 24th January 2017).[9] Mitchell, D.A., Mitchell, L. (2016) Oxford Handbook of Clinical Dentistry, 6th edn., UK: Oxford University Press.[10] Lavender Hill Dental Practice (2014) Implants, Available at: http://www.dentistlocal.co.uk/dental-implants/ (Accessed: 9th February 2017).[11] American Association of Endodontics (2017) Root Canals, Available at: http://www.aae.org/patients/treatments-and-procedures/root-canals/root-canals.aspx (Accessed: 9th February 2017).

Methods

The multipotent nature of mesenchymal stem cells permits them to differentiate into several different cell types [1]. This unique ability has inspired experiments using mice, to investigate whether tooth generation is possibility “for marked changes in future dental therapy” [3].

In order for whole tooth generation, it is important for scientists to recognise a successful combination of epithelial and mesenchymal cells, which release “inductive signals” to one another to initiate the process of whole tooth regeneration [4]. The challenges that scientists are facing include finding “non-embryonic sources of cells with the same properties as tooth germ cells and to develop culture systems that can expand cells that retain tooth forming potential” [5].

Different types of stem cells can be located in the oral cavity and it is important to select the correct cell which incorporates the successful characteristics for tooth regeneration [6]. In one study, human gingival tissue was associated with mesenchymal tissue from embryonic molar teeth of mice (tooth germs). “After 7 days of culture, the re-associations were transplanted into kidney capsules of adult immunocompromised (SCID) mice”.

MircoCT analysis showed 3D formation of tooth-like structures, which had displayed higher density of mineralisation on the coronal part of the structure (corresponding to the enamel of the tooth crown), and a lower density of mineralisation which elongated beyond the coronal section (corresponding to thedentin of the tooth). The tooth-like structures also consisted of a vascularised pulp with cells expressing DSPP (a gene coding for two proteins of the extracellular dentin matrix of the tooth [7]) lining the dentin surface [4].

However, tooth germs from mice were used in this experiment which suggests that there may be problems regarding immune rejection once implanted in humans. Also, an obvious root structure was not expressed in the previous study. A lack of support from the surrounding periodontal structure would result in problems with the longevity of the implant. Another study tried to tackle this issue by theorising a method which would utilise periodontal ligament stem cells, from extracted human wisdom teeth in attempts to regenerate a whole tooth.

Figure 2 showing the process of culturing and implanting whole teeth,which are derived from mesenchymal and epithelial cells [5].

This study developed a method in generating the root of thetooth, separate from the crown. Both structures would then becultured together to produce a whole tooth. The theory wastested using mice, and results showed that the culture not onlydeveloped the roots of the tooth, it was also capable ofproducing periodontal ligament and alveolar bone. The endproduct was a whole mouse tooth, with supporting periodontaltissue. The researchers were able to develop teeth with acorrect morphology, using a collagen sponge to act as ascaffold for the cells. The main idea behind this research wasto produce clinically viable, natural tooth implants withimportant functional characteristics for mastication andocclusion [3].

Studies such as the one previously discussed show that whole tooth regeneration is possible, but depending upon the condition of the patient, surrounding periodontal tissue can also be implanted with the tooth itself. For conditions where these surrounding structures are lacking it can be difficult for successful implantation, thereby limiting the treatments available for the patient. For example, in cases such where a patient is suffering from periodontal disease, the alveolar bone, gingival tissue and periodontal ligaments can become severely destroyed [8]. This may prevent the patient from being able to choose dental implants for a successful treatment option. However, using stem cells to regenerate the surrounding periodontal tissue, gives patients further opportunities.

Figure 3 showing a tooth after root canal treatment, filled with gutta-percha [11].

Not only have stem cells shown possibilities in reproducing whole teeth, developing certain structures within the tooth can also be regenerated for treatment. This was shown in an experiment, when dental pulp stem cells and root apical stem cells were isolated from human third molars and placed into the canal space of root fragments in mice. After 4 months, the root fragments were analysed using a microscope to reveal that the root canal was filled with pulp tissue, with good vascularisation. A mineralised layer of tissue which resembled dentine was also found on the existing walls of the canal [5]. Utilising this procedure in root canal treatment would substitute the use of Gutta-Percha [9], as well as preventing the tooth from becoming devitalised.

another, is mandatory [4]. Also, there needs to be a matrix which would support the growth of the tooth, for example a collagen sponge can used to support tissue growth to resemble a natural tooth [3].

The current standard of research suggests that replacing plastics from treatments isn’t possible. In order for a safe and viable replacement, research must be successfully carried out on human patients first. The fact that experiments have only been carried out mice, with limited success, emphasises the developing nature of this research.

So, can plastics be fully replaced? Not currently. However, harnessing the capabilities of stem cells has immense potential. With success, it has the aptitude to revolutionise dentistry.

References

A mind map was utilised to present and link ideas which would allowed fully exploration regarding whether stem cells and tooth germs are a viable replacement for plastics that would commonly be used by dentists dentists today. In order to increase knowledge and legitimise any points raised, trusted academic papers were used as sources of information. This was done so using Google Scholar and PubMed as search engines for exploring relevant research papers. Once reliable papers were found, I examined their reference page and located more papers which gave access to further information. A Vancouver style of referencing has been used to credit any data from experiments and quotes from research, throughout the poster. The poster itself was constructed using Microsoft PowerPoint.

Shafay Barlas

Figure 1 showing a patient beforeand after the installation of a dentalimplant to replace a missing tooth[10].