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Effective Tooth Repair with Mobilized MSCs!

Review of “Promotion of natural tooth repair by small molecule GSK3 antagonists” from Science Reports by Stuart P. Atkinson

Dental caries represents the most prevalent human disease and leads to the loss of the vital tooth mineral dentine. The mobilization and differentiation of tooth pulp mesenchymal stem cells (MSCs) into odontoblast-like cells, which secrete new dentine [1, 2], can repair small lesions. However, this innate repair strategy cannot heal larger lesions and this necessitates the application of permanent artificial mineral aggregates.

Now, new research from the laboratory of Paul T. Sharpe (Kings College London, UK) may bring the use of artificial substrates for tooth repair to an end! In a new Science Reports paper, Neves et al report the repair of large tooth lesions via the combination of biodegradable and clinically approved collagen sponges (Kolspon) and small molecule-mobilized MSCs [3].

Employing a mouse model, the authors investigated different means to potentiate Wnt/β-cat signaling (associated with the onset of tooth damage) in the hope of mobilizing MSCs and promoting endogenous dentine repair. Treatment of dental pulp MSCs with low doses of the GSK3 inhibitor BIO [(2′Z,3′E)-6-Bromoindirubin-3′-oxime)] offered the best results in terms of effective concentrations and cytotoxicity both in vitro and in vivo.

To test for dentine formation in vivo, the authors created lesions in mouse molar teeth and inserted collagen sponges containing BIO for 4-6 weeks. At the end of this period, the study observed 2 times and 1.7 times higher levels of mineralization when compared to the sponge-only and artificial substrate-only controls, respectively. Furthermore, the experimental treatment produced higher levels of dentine (which covered the entire lesion) with no leftover collagen and, importantly, left the resident dental pulp in a healthy condition.

Will this simple and cost-effective MSC mobilization strategy lead to the end of mineral aggregate filling materials in tooth repair? This study provides evidence of the effectiveness and safety of this novel approach and promotes that assessment of this exciting treatment option towards human trials. 

Keep tuned to the Stem Cells Portal to keep up to date!


  1. Kaukua N, Shahidi MK, Konstantinidou C, et al. Glial origin of mesenchymal stem cells in a tooth model system. Nature 2014;513:551-554.
  2. Feng J, Mantesso A, De Bari C, et al. Dual origin of mesenchymal stem cells contributing to organ growth and repair. Proc Natl Acad Sci U S A 2011;108:6503-6508.
  3. Neves VC, Babb R, Chandrasekaran D, et al. Promotion of natural tooth repair by small molecule GSK3 antagonists. Sci Rep 2017;7:39654.