Periodontal ligament-derived mesenchymal stem cells modulate neutrophil responses via paracrine mechanisms.

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 with Porphyromonas 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)-γ- inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), IFN-γ, 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)-α and IL-1ß 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.

A systematic review and meta-analysis of the survival rate of implants placed in previously failed sites.

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.

Caracterização do efeito imunomodulatório das células mesenquimais indiferenciadas na resposta inflamatória a Porphyromonas gingivalis / Role of periodontal-derived mesenchymal stem cells in Porphyromonas gingivalis infection

O objetivo deste estudo foi caracterizar as respostas das células mesenquimais indiferenciadas derivadas do ligamento periodontal (PDLSCs) ao extrato proteico total de Porphyromonas gingivalis (PgPE) e avaliar seu impacto nas propriedades biológicas das células leucêmicas promielocíticas humanas HL-60. PDLSCs enriquecidas com CD105 foram semeadas em placas de 6 poços durante 24h. Em seguida, as células foram desafiadas com PgPE (0 e 2 mg/ml) durante 3h (período de exposição). Os sobrenadantes foram então descartados; PDLSCs foram lavadas com PBS e cultivadas por 18h adicionais. Por fim, os sobrenadantes foram coletados. Os níveis de citocinas e quimiocinas nos sobrenadantes foram avaliados por ensaios multiplex. Na sequência, o efeito dos sobrenadantes derivados de PDLSCs (tratadas ou não com PgPE) sobre a ativação, o recrutamento e a resposta inflamatória de HL-60 foi avaliado. PDLSCs responderam ao tratamento com PgPE. RANTES, eotaxina e IP-10 (proteína produzida por IFN-?) foram detectados apenas em sobrenadantes de PDLSCs/PgPE. Além disso, PgPE induziu maior secreção de proteína quimiotática de neutrófilos (MCP)-1, intérferon (IFN)-?, interleucina (IL)-6, IL-8 e IL-1ra (p> 0,05). O recrutamento de HL-60D aumentou 4,7 vezes quando estas células foram expostas 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)-? e IL-1? 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.

A systematic review and meta-analysis of the survival rate of implants placed in previously failed sites

Abstract 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.

Efficacy of stem cells on the healing of peri-implant defects: systematic review of preclinical studies.

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.