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Bone Regeneration using Dental Pulp Stem Cells (DPSCs) - a tissue engineering approach


Dental School

About the Project

Aim: The main aim of this project is in vitro regeneration of maxillofacial bone using a tissue engineering technique. Three essential components of this technique are dental pulp stem cells (a rich source of mesenchymal stem cells), bio-material scaffolds and stimulating factors.

The oral cavity is a complex multi-organ structure. Because oral tissues and organs are functionally connected at many levels, irreversible damage to any of them is likely to eventually affect the others, causing extensive malfunction. Tooth decay, periodontal disease, alveolar bone resorption, orthodontic problems, orofacial neuropathic pain and impaired salivary gland function are conditions that seriously affect oral health of a large part of the world population. Owing to their functional connectivity, once damage is diagnosed in one organ of the oral cavity, it is important to intervene rapidly and efficiently, to repair or replace the injured or lost tissues, to avoid severe degradation of oral health.

Synthetic replacement materials and prostheses (fillings, bridges, implants, etc.) have traditionally been the treatment of choice to treat dental decay. However, all functions of the original biological tooth are not fully restored by this kind of replacement therapies. Thus, tissue engineering represents a new collection of treatment options for the complete biological regeneration of cranio-maxillofacial tissues and organs. Tissue engineering is now fully considered as an alternative to the conventional treatments for dental injury and disease, offering substantial advantages over traditional dental restoration techniques (Nör, 2006; Wang et al., 2012).

Stem cells are the cornerstone of regenerative cell therapy. In the oral cavity, adult tooth tissues also contain different active populations of stem cells with a mesenchymal phenotype (Huang et al., 2009). Unlike other types of MSC, dental stem cells originate from the neural crest (Janebodin et al., 2011) and are lineage-related with peripheral nerve glial progenitor cells (Kaukua et al., 2014), which places them in a privileged position to mediate regeneration of both connective and nerve tissues (Ibarretxe et al., 2012; Martens et al., 2013). Several types of human dental stem cells have been identified. Among them; DFPC, Dental Follicle progenitor cells; PDLSC, Periodontal ligament stem cell; SCAP, Stem cells from apical papilla; SHED ,Stem cells from primary exfoliated deciduous teeth; DPSC, Dental pulp stem cells, which are without a doubt the most used for research purposes. The osteogenic differentiation capacity of DPSCs has been well demonstrated in vitro, with strong alkaline phosphatase (Lindroos et al., 2008) and expression of bone-specific markers within newly formed bone (d’Aquino et al., 2007, 2008).

The aim of this project is to regenerate cranial, maxillary and mandibular bone which is essential in the field of implantology and craniofacial deformity. We will utilise dental pulp stem cells together with the different scaffold biomaterials and stimulating factor combinations to elicit an optimal cellular response required to regenerate damaged bone tissue. Cells from the dental pulp will be extracted and isolated in Tecnologica Research Institute, Crotone, Italy (Collaborator: Dr Marco Tatullo). Cells will then be characterised for mesenchymal stem-cell type properties by Flow Cytometry and will be sorted by Fluorescence-assisted Cell Sorting (FACS) in Dundee. Osteogenic differentiation studies using scaffold biomaterials and growth factors will be carried out subsequently.

For informal enquiries about the project, contact Dr Mohammad Islam ()
For general enquiries about the University of Dundee, contact


QUALIFICATIONS
Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK in a relevant discipline.

English language requirement: IELTS (Academic) score must be at least 6.5 (with not less than 5.5 in each of the four components). Other, equivalent qualifications will be accepted. Full details of the University’s English language requirements are available online: http://www.dundee.ac.uk/guides/english-language-requirements.


APPLICATION PROCESS

Step 1: Email Dr Mohammad Islam () to (1) send a copy of your CV and (2) discuss your potential application and any practicalities (e.g. suitable start date).

Step 2: After discussion with Dr Islam, formal applications can be made via UCAS Postgraduate:

Apply for the PhD in the Dental School: https://digital.ucas.com/coursedisplay/courses/1e6f404e-f563-7944-91e8-2415b17a5347. Select the start date and study mode (full-time/part-time) agreed with the lead supervisor.

In the ‘provider questions’ section of the application form:
- Write the project title and ‘FindAPhD.com’ in the ‘if your application is in response to an advertisement’ box;
- Write the lead supervisor’s name and give brief details of your previous contact with them in the ‘previous contact with the University of Dundee’ box.

In the ‘personal statement’ section of the application form, outline your suitability for the project selected.

Funding Notes

There is no funding attached to this project. The successful applicant will be expected to provide the funding for tuition fees and living expenses, via external sponsorship or self-funding.

References

d’Aquino R, De Rosa A, Lanza V et al. 2009; Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. Eur Cell Mater 18: 75–83.

d’Aquino R, Papaccio G, Laino G et al. 2008; Dental pulp stem cells: a promising tool for bone regeneration. Stem Cell Rev 4:21–26.

Huang,G.T., Gronthos,S., and Shi,S.(2009).Mesenchymal stem cells derived from dental tissues vs. those from other sources :their biology and role in regenerative medicine. J. Dent. Res. 88,792–806.doi: 10.1177/0022034509340867

Ibarretxe,G.,Crende,O.,Aurrekoetxea,M.,García-Murga,V.,Etxaniz,J.,and Unda,F.(2012).Neural crest stem cells from dental tissues: a new hope for dental and neural regeneration. Stem Cells Int. 2012:103503.doi:10.1155/2012/ 103503

Janebodin,K.,Horst,O.V.,Ieronimakis,N.,Balasundaram,G.,Reesukumal,K., Pratumvinit, B., et al.(2011). Isolation and characterization of neural crest- derived stem cells from dental pulp of neonatal mice. PLoSONE 6:e27526.doi: 10.1371/journal.pone.0027526

Kaukua,N.,Shahidi,M.K.,Konstantinidou,C.,Dyachuk, V., Kaucka,M., Furlan, A., et al.(2014). Glial origin of mesenchymal stem cells in a tooth model system. Nature 513,551–554.doi:10.1038/nature13536

Lindroos B, Mäenpää K, Ylikomi T et al. 2008; Characterisation of human dental stem cells and buccal mucosa fibroblasts. Biochem Biophys Res Commun, 368: 329–335.

Martens,W.,Bronckaers,A.,Politis,C.,Jacobs,R.,andLambrichts,I.(2013). Dental stem cells and their promising role in neural regeneration: an update. Clin.Oral Invest. 17,1969–1983.doi:10.1007/s00784-013-1030-3

Nör, J.E.(2006).Tooth regeneration in operative dentistry. Oper. Dent. 31, 633–642.doi:10.2341/06-000

Wang,Y.,Preston,B.,andGuan,G.(2012).Tooth bioengineering leads the next generation of dentistry. Int. J. Paediatr. Dent. 22,406–418.doi:10.1111/j.1365- 263X.2011.01206.x

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