Intracellular Bacteria in Stem Cells of the Apical Papilla: A “Trojan Horse” for Regenerative Endodontic Failure
Bibliographic record
Abstract
INTRODUCTION: Regenerative endodontic procedures show unpredictable outcomes in infected teeth due to persistent infection. While current disinfection protocols reduce but do not eliminate root canal bacteria, the fate of residual microorganisms during stem cell recruitment remains unclear. This study tested the hypothesis that endodontic pathogens invade and survive within stem cells of the apical papilla (SCAP), diminishing its biomineralization potential. METHODS: Internalization of SCAP by Gram-positive (Enterococcus faecalis, Actinomyces naeslundii) and Gram-negative (Porphyromonas gingivalis, Fusobacterium nucleatum) bacteria was characterized using colony-forming unit assays, confocal microscopy and flow cytometry. Intracellular survival of E. faecalis was monitored for 14 days in both planktonic and biofilm phases. The impact of intracellular E. faecalis on SCAP biomineralization and odontogenic differentiation was assessed using alkaline phosphatase activity, alizarin red staining, and quantitative real-time PCR. Statistical analyses were performed using one-way ANOVA with Dunnett's multiple comparison test or two-way ANOVA with Tukey's multiple comparison test. P < .05 was considered statistically significant. RESULTS: All tested bacteria invaded SCAP with differential efficiencies. E. faecalis and F. nucleatum demonstrated robust internalization (∼5-log colony forming unit), while P. gingivalis and A. naeslundii showed reduced invasion (∼2.5 log colony forming unit). E. faecalis persisted intracellularly for up to 14 days, with biofilm-phase bacteria showing enhanced survival in monolayer SCAP cultures. Intracellular E. faecalis abrogated SCAP mineralization while maintaining cell viability, accompanied by significant downregulation of all tested odontogenic genes (P < .05). CONCLUSIONS: Bacteria invade and establish persistent intracellular infections within SCAP, creating protected reservoirs. These intracellular bacteria severely compromise odontogenic differentiation without killing the host cells, representing a potentially unrecognized mechanism of regenerative endodontic procedure failure. This "Trojan horse" strategy may explain the unpredictable outcomes of regenerative endodontics in infected teeth.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".