Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters.

Oral mesenchymal stem/progenitor cells (MSCs) are renowned in the field of tissue engineering/regeneration for their multilineage differentiation potential and easy acquisition. These cells encompass the periodontal ligament stem/progenitor cells (PDLSCs), the dental pulp stem/progenitor cells (DPSCs), the stem/progenitor cells from human exfoliated deciduous teeth (SHED), the gingival mesenchymal stem/progenitor cells (GMSCs), the stem/progenitor cells from the apical papilla (SCAP), the dental follicle stem/progenitor cells (DFSCs), the bone marrow mesenchymal stem/progenitor cells (BM-MSCs) from the alveolar bone proper, and the human periapical cyst-mesenchymal stem cells (hPCy-MSCs). Apart from their remarkable regenerative potential, oral MSCs possess the capacity to interact with an inflammatory microenvironment. Although inflammation might affect the properties of oral MSCs, they could inversely exert a multitude of immunological actions to the local inflammatory microenvironment. The present review discusses the current understanding about the immunomodulatory role of oral MSCs both in periodontitis and systemic diseases, their "double-edged sword" uniqueness in inflammatory regulation, their affection of the immune system, and the underlying mechanisms, involving oral MSC-derived extracellular vesicles.

Stem/progenitor cell-mediated pulpal tissue regeneration: a systematic review and meta-analysis.

BACKGROUND: Stem/progenitor cell-mediated pulpal regeneration could represent a promising therapeutic alternative in the field of clinical endodontics. AIM: The present study aimed to systematically assess and meta-analyse dental pulpal tissue regeneration, pulpal vitality and apical healing after the transplantation of stem/progenitor cells versus no transplantation. DATA SOURCES: MEDLINE, Cochrane CENTRAL and EMBASE were searched up to January 2019 for animal experiments and human trials evaluating the pulpal transplantation of stem/progenitor cells. Cross-referencing and hand search were additionally performed. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Based on randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs), conducted in animals or humans, the effect of the transplantation of stem/progenitor cells compared to no transplantation on pulpal tissue regeneration, pulpal vitality and apical healing was examined. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was histologically determined pulpal tissue regeneration, whilst pulpal vitality and apical healing were secondary outcomes. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) guidelines and the revised Cochrane risk of bias tool (RoB 2.0) were used for risk-of-bias assessment. Pooled standardized differences in means (SDM) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analyses. RESULTS: From 2834 identified articles, eight animal experiments (82 animals with 336 experimental pulpal defects) and one human trial (40 humans with 40 pulpal defects) were included. Risk of bias of most animal studies was high, whilst the human trial revealed 'some concerns'. Stem/progenitor cell-transplanted pulps demonstrated significantly increased pulpal tissue regeneration compared with controls (SDM [95%CI]: 6.29 [3.78-8.80]). LIMITATIONS: Data on pulpal vitality and apical healing were sparse and inconsistent. Heterogeneity across studies was substantial, publication bias was present, and mainly indirect, surrogate outcome measures were applied. The overall strength of evidence was very low. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The transplanation of stem/progenitor cells shows promise for pulp regeneration, whilst clinical routine application is still not in reach. Further investigations, employing a comprehensive set of outcomes including those demonstrating functional pulp regeneration relevant for patient-centred care, are required.

Effect of total sonicated Aggregatibacter actinomycetemcomitans fragments on gingival stem/progenitor cells.

BACKGROUND: Aggregatibacter-actinomycetemcomitans (A.actinomycetemcomitans) are strongly associated with localized-aggressive-periodontitis (LAgP). The study's aim was to test for the first time the effect of total sonicated A.actinomycetemcomitans-bacterial-fragments on gingival mesenchymal stem/progenitor cells' (G-MSCs) proliferation and regenerative gene expression in-vitro. MATERIAL AND METHODS: G-MSCs were isolated, characterized, expanded and stimulated by total sonicated A.actinomycetemcomitans-bacterial-fragments (0 (negative-control), 15, 60, 120 and 240µg/ml; serovar-b; n=6/group). Cellular proliferation and NF-κß (NFKB1), Alkaline Phosphatase (ALPL), Collagen-I (COL1A1), Collagen-III (COL3A1), Osteonectin (SPARC) and Osteopontin (SPP1) m-RNA expression were assessed via reverse-transcription-polymerase-chain-reaction (RT-PCR) at 24, 48 and 72 hours and CFUs-ability evaluated at twelve days. RESULTS: G-MSCs demonstrated stem/progenitor cells' characteristics. A.actinomycetemcomitans-bacterial-fragments (up to 72 hours) resulted in marked G-MSCs' proliferation over-time (p<0.001) and elevated NFKB1 (p=0.017), COL1A1 (p=0.025), SPARC (p=0.025), decreased ALPL (p=0.017), with no significant differences for COL3A1 and SPP1 expression or stimulation times (p>0.05; Friedman-test). Longer-term stimulation for twelve days reduced G-MSCs' CFUs. CONCLUSIONS: Sonicated A.actinomycetemcomitans-bacterial-fragments' exert beneficial short-term effects on G-MSCs' proliferative and non-mineralized tissue forming aptitude. Results shed new light on the importance of periodontal treatment for LAgP patients, using power driven sonic/ultrasonic devices, which, in addition to reducing the subgingival microbial load, produces cell-stimulatory A.actinomycetemcomitans-bacterial-fragments, with positive attributes on tissue reparative/regenerative responses of tissue resident stem/progenitor cells in their niche.

Adult mesenchymal stem cells explored in the dental field.

During the last decade it was realized that stem cell-based therapies hold an enormous therapeutic potential, improving the life of patients with conditions ranging from neurodegenerative and traumatic diseases to regenerative medicine requiring replacement of complex structures such as bones and teeth. Based on their ability to regenerate and/or repair damaged tissue and eventually restore organ function, multiple types of stem/progenitor cells have been discovered. In the field of periodontal regeneration and tooth engineering, several types of adult multipotent mesenchymal stem cells from various sources are currently being investigated. These include the bone marrow stromal stem cells (BMSSCs), adipose-derived stromal cells (ADSCs), dental pulp stem cells (DPSCs), dental follicle stem cells (DFSCs), stem cells from human exfoliated deciduous teeth (SHEDs), stem cells from the apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), alveolar bone proper-derived stem cells, and gingival stem cells. The potential of these different MSCs as precursors for regenerative purposes in the dental field is discussed in this chapter.