Potential of Mesenchymal Stem Cell Sheets on Periodontal Regeneration: A Systematic Review of Pre-Clinical Studies

Abstract

Background: Cell sheet technique using mesenchymal stem cells is a high-level strategy in periodontal regenerative medicine. Although recent studies have shown the role of MSCSs in increased dental supporting tissues and bone, there is not a systematic review focused specifically on assessing periodontal regeneration in orthotopic animal models. Objective: To evaluate the potential of mesenchymal stem cell sheets (MSCSs) on periodontal regeneration, compared to control, in experimental animal models. Methods: Pre-clinical studies in periodontal defects of animal models were considered eligible. The electronic search included the MEDLINE, Web of Science, EMBASE and LILACS databases. The review was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement guidelines. Results: A total of 17 of the 3989 studies obtained from the electronic database search were included. MSCSs included dental follicle (DF) MSCSs, periodontal ligament (PL) MSCSs, dental pulp (DP) MSCSs, bone marrow (BM) MSCSs, alveolar periosteal (AP) MSCSs and gingival (G) MSCSs. Regarding cell sheet inducing protocol, most of the studies used ascorbic acid (58.82%). Others used culture dishes grafted with a temperature-responsive polymer (41.18%). Adverse effects were not identified in the majority of studies. Meta-analysis was not considered because of methodological heterogeneities. PDL-MSCSs demonstrated to be superior for periodontal regeneration enhancement compared to control, but in an induced inflammatory microenvironment, DF-MSCSs were better. Moreover, DF-MSCSs, DP-MSCSs, and BM-MSCSs showed improved results compared to control. Conclusion: MSCSs can improve periodontal regeneration in animal periodontal defect models.

Osteogenesis in human periodontal ligament stem cell sheets is enhanced by the protease-activated receptor 1 (PAR1) in vivo

“…Periodontal ligament tissue specimens were obtained through the scaling of the middle third of the root and PDLSCs were isolated using the explant technique 12 , 48 in alpha-modified Eagle’s medium (α-MEM) (Thermo Fisher Scientific, Waltham, USA) supplemented with 10% fetal bovine serum (FBS) (Thermo Fisher Scientific, Waltham, USA), 100 μg/mL penicillin, 100 μg/mL streptomycin, and 0.5 mg/mL amphotericin B (Gibco, Invitrogen, Carlsbad, USA) at 37 °C in an atmosphere of 5% CO2 and 95% humidity 7 . After 14 days, cells from the explants achieved a 70% confluence degree and PDLSCs populations were used in passage 4 for all experiments.…”

“…PDLSCs at 1 × 10 6 cells/cm2 were seeded in 100 mm plates for 24 h with α-MEM (Thermo Fisher Scientific, Waltham, USA) supplemented with 10% of FBS (Thermo Fisher Scientific, Waltham, USA) and 50 μg/mL vitamin C to induce cell sheet formation, as previously described 7 . Subsequently, cell sheets were assigned for one of the following experimental groups: (1) control medium (CTRL) composed of α-MEM (Thermo Fisher Scientific, Waltham, USA) supplemented with 10% of FBS (Thermo Fisher Scientific, Waltham, USA) and 50 μg/mL vitamin C (Sigma-Aldrich, St Louis, USA); (2) osteogenic medium (OST) (CTRL + 100 nM dexamethasone, 5 mM b-glycerophosphate and 50 µg/ml ascorbic acid (Sigma-Aldrich, St Louis, USA) and (3) osteogenic medium with the addition the PAR 1 agonist peptide (100 nM TFLLR-NH2) (Tocris Bioscience Inc., Bristol, UK) (OST + PAR 1 ).…”

“…Recently, several studies in the cell-based regenerative medicine field have been reported combining tissue engineering and stem cells 5 – 7 . The use of cell sheets is a promising therapeutic strategy that allows the use of mesenchymal stem cells in a construct that maintains interconnected cells in contact with their extracellular matrix, providing stability and allowing delivery to possible therapies 8 .…”

Can vitamins improve periodontal wound healing/regeneration?

“…Anatomically, it is responsible for the dento-alveolar homeostasis and function and is comprised of four tissues of divergent embryological origins, namely the alveolar bone, the cementum, the gingiva, and the periodontal ligament. 1 An intricate attachment of these tissues results from a sequence of synchronized compound interactions between neural crest ecto-mesenchymal and epithelial cellular components during embryogenesis. 2 Divergent cellular populations reside in the mature functional periodontium, comprising cementoblasts, endothelial cells, epithelial cells, fibroblasts, nerve cells, osteoblasts, in addition to a minor population of stem/progenitor cells.…”

“…Apart from firstly enhancing cellular metabolism and Sox2 and Oct4A pluripotency gene expression, inflammation seemed to reduce these AA-induced positive effects 177. AA was further extensively applied in the biosynthesis of cell sheets of mesenchymal stem cells from the bone marrow, umbilical cord, stem cells from the apical papilla (SCAP), PDLSCs, and human dental pulp stem cells (DPSCs), with great potential in periodontal regenerative approaches 1. AA at concentrations of 20 μg/mL predictably produced cell sheets from SCAP, PDLSCs, and DPSCs, with upregulated expressions of the pluripotency markers OCT4, SOX2…”