This systematic review aims to evaluate mesenchymal stem cells (MSC) periodontal regenerative potential in animal models. MEDLINE, EMBASE and LILACS databases were searched for quantitative pre-clinical controlled animal model studies that evaluated the effect of local administration of MSC on periodontal regeneration. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. Twenty-two studies met the inclusion criteria. Periodontal defects were surgically created in all studies. In seven studies, periodontal inflammation was experimentally induced following surgical defect creation. Differences in defect morphology were identified among the studies. Autogenous, alogenous and xenogenous MSC were used to promote periodontal regeneration. These included bone marrow-derived MSC, periodontal ligament (PDL)-derived MSC, dental pulp-derived MSC, gingival margin-derived MSC, foreskin-derived induced pluripotent stem cells, adipose tissue-derived MSC, cementum-derived MSC, periapical follicular MSC and alveolar periosteal cells. Meta-analysis was not possible due to heterogeneities in study designs. In most of the studies, local MSC implantation was not associated with adverse effects. The use of bone marrow-derived MSC for periodontal regeneration yielded conflicting results. In contrast, PDL-MSC consistently promoted increased PDL and cementum regeneration. Finally, the adjunct use of MSC improved the regenerative outcomes of periodontal defects treated with membranes or bone substitutes. Despite the quality level of the existing evidence, the current data indicate that the use of MSC may provide beneficial effects on periodontal regeneration. The various degrees of success of MSC in periodontal regeneration are likely to be related to the use of heterogeneous cells. Thus, future studies need to identify phenotypic profiles of highly regenerative MSC populations.

This systematic review considers the evidence from animal studies evaluating the effectiveness of mesenchymal stem cells (MSC) in the treatment of intraoral peri‐implant defects. MEDLINE, EMBASE, and LILACS databases were searched for quantitative preclinical controlled animal model studies that evaluated the effect of MSC on bone healing at intraoral peri‐implant bone defects. The primary outcome was the amount of (re‐)osseointegration reported as bone‐to‐implant contact in the defect area. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement guidelines. Ten studies met the inclusion criteria. Only one study induced peri‐implant inflammation to produce peri‐implant bone defects. In all others, defects were surgically created at implant installation. Differences in defect morphology were identified among the studies. Both xenogenous and autogenous MSC were used to treat peri‐implant defects. These included bone marrow‐derived MSC, periodontal ligament‐derived MSC, umbilical cord MSC, bone marrow‐derived mononuclear cells, and peripheral blood mononuclear cells. Meta‐analysis was not possible because of heterogeneities in study designs. Nonetheless, in most studies, local MSC implantation was not associated with adverse effects and had a positive effect on bone healing around peri‐implant defects. Combination of MSC with membranes and bioactive factors appears to provide improved treatment outcomes. In large animal models, intraoral use of MSC may provide beneficial effects on bone healing within peri‐implant defects. The various degrees of success of MSC in peri‐implant bone healing are likely to be related to the use of cells from various populations, tissues, and donor species. However, human safety and efficacy must be demonstrated before its clinical use can be considered.

Background: Mesenchymal stem cells differentiate into distinct mesenchymal cell lineages and regulate the immune response. The aim of this study was to determine whether periodontal ligament-derived mesenchymal stem cells (PDLSCs) have the ability to modulate neutrophil responses via paracrine mechanisms. Methods: CD105-enriched PDLSCs were seeded for 24 h and challenged withPorphyromonas gingivalis total protein extract (PgPE) (0 or 2 ug/mL) for 3 h. Cells were then washed and further cultured for 18 h and the supernatants were collected and stored. Next, neutrophil-differentiated human promyelocytic leukemia HL-60 cells (HL60D) were treated with PDLSCs supernatants and HL-60D activation and functional responses were determined.Results: PgPE treatment induced higher secretion of inflammatory markers and chemokines by PDLSCs, including RANTES, eotaxin, interferon (IFN)--inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), IFN-, interleukin (IL)-6, IL-8 and IL-1ra (P < 0.05). HL-60D recruitment rate was increased by 4.7 ± 1.09-fold when exposed to PgPE-treated PDLSCs supernatants. PgPE-treated PDLSCs supernatants promoted a 1.78 ± 1.04-fold increase in the production of intracellular reactive oxygen species (ROS) by PMA-stimulated HL-60D, whereas PgPE-untreated PDLSCs supernatants led to a 16% reduction in intracellular ROS. In sharp contrast, neither PgPE-untreated nor PgPE-treated PDLSCs supernatants altered tumor necrosis factor (TNF)-and IL-1 secretion by HL-60D cells.Conclusion: Together, these findings suggest an important role of PDLSCs in the recognition of P. gingivalis, paracrine recruitment and activation of antimicrobial mechanisms in innate immune cells, without interfering in cytokine responses. K E Y W O R D Scellular biology, inflammation, innate immune responses, neutrophils, reactive oxygen species * Sigma Chemical, St. Louis, MO † ATCC, Manassas, VA

The aim of this study was to conduct a systematic review and meta-analysis to assess the clinical outcomes of dental implants placed in previously early and late implant failed sites. An electronic literature search was conducted in several databases for articles published up to February 2018. Human clinical trials that received at least one implant in a previously failed site were included. Hence, the PICO question that was aimed to be addressed was: Do patients undergoing implant replacement (second and third attempts) in previous failed sites have survival rates similar to implants placed at first attempts? A random effects model was used to calculate survival weighted means and corresponding 95% Confidence Intervals (CI) among studies. Eleven studies of low to moderate methodological quality were included in this review. Implants placed in sites with history of one and two implant failures had a weighted survival rate (SR) of 88.7% (95%CI 81.7-93.3) and 67.1% (95%CI 51.1-79.9), respectively. Implants placed in sites with a previous early failure revealed a weighted SR of 91.8% (95%CI 85.1-95.6). First implants presented higher SR than implants placed in sites with one or two previous implant failures. In contrast, implants placed in sites with one and two implant failures had similar SR. Within its limitations, this review suggests that replacement implants have moderate SR. Larger prospective studies with well-defined criteria for early and late implant failure are necessary to confirm and expand on these results.

a sobrenadantes PDLSCs/PgPE, enquanto que os sobrenadantes de PDLSCs não afetaram a quimiotaxia de HL-60D. Sobrenadantes PDLSCs promoveram uma redução de 16% na produção de espécies de oxigênio reativo (ROS) por HL-60D estimuladas por PMA (p=0,013). Em contraste, sobrenadantes PDLSCs/PgPE promoveram um aumento de 1,78±1,04 vezes (p=0,046) na produção de ROS. Finalmente, tanto sobrenadantes PDLSCs, como sobrenadantes PDLSCs/PgPE, não influenciaram a produção de fator de necrose tumoral (TNF)-α e IL-1β pelas HL-60D em resposta ao lipopolissacarídeo (LPS). Esses achados sugerem um importante papel das PDLSCs no reconhecimento de P. gingivalis, recrutamento de células imunes inatas e ativação de mecanismos antimicrobianos. Palavras-chave: células tronco, Porphyromonas gingivalis, neutrófilos, inflamação. ABSTRACT Misawa MYOM. Role of periodontal-derived mesenchymal stem cells in Porphyromonas gingivalis infection [thesis]. São Paulo: Universidade de São Paulo, Faculdade de Odontologia; 2018. Versão Corrigida.The aim of this study was to characterize periodontal ligament-derived mesenchymal stem cells (PDLSCs) responses to Porphyromonas gingivalis total protein extract (PgPE) and its impact on human leucocyte promyelocyte cells HL-60 biological properties. CD105-enriched PDLSCs were seeded in 6-well plates for 24h. Next, cells were challenged with PgPE (0 and 2mg/ml) for 3h (exposure period). Supernatants were then discarded, cells were washed with PBS, and cultured further for 18h before supernatants were collected. Supernatants' cytokine and chemokine levels were assessed by bead-based multiplex assays. The effect of supernatants collected from untreated and PgPE-treated PDLSCs on HL-60D activation, recruitment and inflammatory responses was determined. PDLSCs were responsive to PgPE treatment. RANTES, eotaxin, and interferon-inducible protein (IP)-10 were detected only in supernatants collected from PgPE treated cells. Moreover, PgPE induced higher monocyte chemoattractant protein (MCP)-1, interferon (IFN)-γ, interleukin (IL)-6, IL-8 and IL-1ra secretion (p > 0.05). HL-60D recruitment was increased by 4.7 fold when exposed to PDLSCs/PgPE supernatants, whereas PDLSCs supernatants did not affect HL-60D chemotaxis. PDLSCs supernatants promoted a 16% reduction in radical oxygen species (ROS) production by PMA-stimulated HL-60D (p=0.013). On the contrary, PDLSCs/PgPE supernatants promoted a 1.78 ± 1.04 fold increase (p=0.046) in ROS production. Finally, both PDLSCs and PDLSCs/PgPE supernatants had no effect on HL-60D tumor necrosis factor (TNF)-α and IL-1β responses to lipopolysaccharide (LPS). These findings strongly suggest an important role of PDLSCs in the recognition of P gingivalis, recruitment of innate immune cells and activation of antimicrobial mechanisms.