Mesenchymal stem cells in periodontal regeneration?


Periodontitis is a common disease that can result in the progressive and irreversible destruction of the periodontal supportive tissues, including gingiva, periodontal ligament, cementum, and alveolar bone. Periodontal treatment is geared towards stopping progression and ideally regenerating the original form and function of the periodontal tissues.  A number of treatments have been used to achieve regeneration including guided tissue regeneration, enamel matrix derivative, bone grafts, growth factors, or combinations thereof.  Recently cell-based approaches using mesenchymal stem cell populations have been tested

The aim of this review was to evaluate the potential efficacy of mesenchymal stem cells in periodontal regeneration in humans on the following main outcomes; clinical attachment level probing depth and gingival recession.


Searches were conducted in the PubMed/Medline, Embase, Cochrane Library, and IRSCTN ( databases. Studies conducted in health adults with periodontal disease involving the use of mesenchymal stem cells (MSCs) in periodontal regeneration were considered. All types of defined MSCs were included.  The primary outcomes considered were he rate of increase in alveolar bone height (radiographic parameter) and the clinical attachment level (CAL).   Initially a qualitative review including all study designs was performed followed by a meta-analysis involving only randomised controlled trials (RCTs). Two reviewers independently selected studies, extracted data and assessed risk of bias using the Cochrane tool.  Pooled mean differences and 95% confidence intervals (CIs) were calculated for primary and secondary outcomes.


  • 15 studies involving 123 patients and 158 periodontal defects were included.
  • The studies included 1 phase I/II trial, 9 case reports/ series, 1 observational study, 1 retrospective pilot study, and 3 RCTs.
  • 13 studies treated intrabony defects and 3 studies treated furcation defects.
  • Stem cells were administered alone (one study), with a scaffold (10 studies), with bovine-derived bone mineral materials (Bio-Oss®) (one study), and/or with platelet-rich plasma (PRP) (3 studies).
  • All 15 included studies reported improvements in CAL, a mean PD reduction, gingival recession changes, and radiographic bone filling.
  • 2 RCTs involving 59 patients (70 periodontal defects) were included in a meta-analysis.
  • Both RCTs were considered to be at high risk of bias.
  • Meta-analysis found a statistically significant difference in favour of stem cell use for CAL but not for PD or gingival recession (GR).
    • CAL; MD = −0.90 mm (95%CI; −1.51; −0.29)
    • PD;   MD = −0.57 mm (95%CI; −1.57; 0.43)
    • GR;  MD = −0.21 mm (95%CI; −0.67; 0.24)


The authors concluded: –

Low-quality evidence suggests that MSC-based therapy may have a small impact on periodontal regeneration. However, due to the monocentric character, the small sample size, and potential heterogeneity across the two included RCTs, these results must not be considered as definitive. High-quality RCTs are needed before any clinical use of MSCs in periodontal regeneration.


The reviewers have searched a good range of databases although they have restricted their time frame to a very short period from October 2017 up to June 2018. While the use of stem cells is a relatively new innovation starting the search a little earlier may have been beneficial.  Consequently only 15 studies were identified, only 3 of these were RCTs with only two of these contributed to the meta-analysis.   The currently available data is both limited in patient numbers and the quality of the available studies. While this might be expected of a new technology there will be a need for high-quality well reported RCTs to assess effectiveness before this technology enters general clinical use as reflected in the authors’ conclusion.


Primary Paper

Novello S, Debouche A, Philippe M, Naudet F, Jeanne S. Clinical application of mesenchymal stem cells in periodontal regeneration: A systematic review and meta-analysis. J Periodontal Res. 2019 Aug 4. doi: 10.1111/jre.12684. [Epub ahead of print] Review. PubMed PMID: 31378933.

Review protocol on PROSPERO

Other references

Dental Elf – 24th Jul 2017

Periodontal regeneration therapies: Are benefits long-term?







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