Secreted products of oral bacteria and biofilms impede mineralization of apical papilla stem cells in TLR-, species-, and culture-dependent fashion

Abstract

Regenerative endodontics exploits the mineralization potential of stem cells from the apical papilla (SCAPs) in order to promote root maturation of permanent immature teeth. SCAPs may encounter post-disinfection residual bacteria either in planktonic or in biofilm growth mode. Bacterial components bind to Toll-like receptors (TLRs) and trigger pro-inflammatory responses. We hypothesized that biofilm-triggered TLR activation affects the mineralization potential of human SCAPs. SCAPs were challenged with conditioned media derived from standardized dual-species biofilms and planktonic bacterial cultures and their inflammatory status and mineralization capacity were studied. Bacterial products from both growth modes (planktonic vs. biofilm) compromised cell viability, proliferation and mineralization capacity of SCAPs, but in a species- and growth mode-dependent fashion. While TLR4 expression remained unaffected, TLR2 expression was upregulated coinciding with a pro-inflammatory activation of SCAPs. Moreover, TLR and its downstream TGF-β-associated kinase (TAK1) appeared to be blocking mineralization, as inhibition of these factors restored it. In conclusion, bacterial products promoted the pro-inflammatory status and inhibited mineralization of human SCAPs in a TLR-, species-, and culture-dependent fashion. TLR2 emerged as the pivotal mediator of these responses and further research is warranted towards the judicious manipulation of SCAPs in order to modify the untoward events of TLR-priming and signaling.

Cytokine Secretion, Viability, and Real-Time Proliferation of Apical-Papilla Stem Cells Upon Exposure to Oral Bacteria

“…Adult or somatic stem cells of dental origin have raised interest for potential use in regenerative endodontics, including root formation ( Yang et al., 2017 ). These cells, mainly located in the most apical part of the dental papilla, SCAP, may be compromised in the presence of bacteria ( Chatzivasileiou et al., 2015 ; Petridis et al., 2018 ). Thus, the oral cavity is highly populated by a complex ecosystem of bacterial species ( Deo and Deshmukh, 2019 ) underlying the interaction between cells and bacteria.…”

New Insights into the Microbial Profiles of Infected Root Canals in Traumatized Teeth

“…RET has shown very promising results as it is a tissue regenerative procedure that promotes continued root development by stem cells [9,10]. However, one of the main challenges in RET is the persistence of microorganisms in the pulpal space, even after disinfection regimens [11], a fact that may have adverse effects in stem cells function [12]. Hence, knowledge of the microbiota profiles of traumatized teeth can be essential for treatment success.…”

Atomic Force Microscopy (AFM) As a Surface Mapping Tool in Microorganisms Resistant Toward Antimicrobials: A Mini-Review

“…For example, the cell walls of resistant bacterial strains in general elicit greater stiffness and thickness ( Tajkarimi et al., 2016 ) that deter the intracellular traffic of antimicrobial molecules, resulting in reduced drug efficacy. Similarly, due to increased adhesiveness, resistant bacteria are known to aggregate in densely packed layer(s) on biomaterials and produce biofilms due to both non-specific (e.g., acid-base and van der Waals) and specific (receptor-mediated binding to ligands) interactions ( King and Korolik, 2017 ; Senneby et al., 2017 ; Carniello et al., 2018 ; Petridis et al., 2018 ), as reported for Staphylococcus aureus/epidermidis , Pseudomonas aeruginosa , Porphyromonas gingivalis , Treponema denticula , and Tanerella forsythia —the causative agents of infections refractory to antimicrobial therapy in cystic fibrosis (CF), endocarditis, osteomyelitis, sinusitis, otitis media, and nosocomial infections. An in-depth understanding of the cellular nanomechanical properties, including quantification of adhesive forces with nanoscale resolution and detection of molecular fingerprints and surface topography, have been hypothesized to be a strategy for identifying and then isolating resistant strains ( Baptista et al., 2018 ).…”