Delivery of Apical Mesenchymal Stem Cells into Root Canals of Mature Teeth

Abstract

Regenerative endodontic procedures are stem cell-based treatments for immature teeth with pulp necrosis. The translation of regenerative endodontic procedures into treating mature teeth depends, among other factors, on the availability and delivery of mesenchymal stem cells (MSCs) into the root canal system. The aim of this clinical study was to evaluate whether evoked bleeding from the periapical tissues elicits the influx of MSCs into the root canal system in mature teeth with apical lesions. Participants included in this study (N = 20) were referred for endodontic treatment of mature teeth with apical lesions. Following chemomechanical debridement, intracanal bleeding from the periapical tissues was achieved, and intracanal blood samples were collected. A positive blood aspirate was also collected in the cartridges during local anesthesia. Total RNA was isolated and used as a template in quantitative reverse transcription polymerase chain reactions using MSC-specific arrays. Data were analyzed with the Wilcoxon signed-rank test, and correlation between gene expression and sex or age was tested with Spearman's rank correlation coefficient test. In addition, MSCs were isolated from an intracanal bleeding sample and subjected to flow cytometry and quantitative osteogenesis assay. Last, the presence and distribution of MSCs within periradicular lesions were evaluated with immunohistochemistry (n = 4). The MSC markers CD73, CD90, CD105, and CD146 were significantly upregulated, with median fold change values of 2.9, 31.7, 4.6, and 6.8, respectively. Conversely, the negative marker for MSCs, CD45, was significantly downregulated (median, -2.7). There was no correlation with age, sex, tooth type, or treatment for any of the evaluated genes. Isolated intracanal cells coexpressed MSC markers and demonstrated robust mineralizing differentiation potential. Finally, immunohistochemical analysis revealed that MSCs were found compartmentalized mainly within vasculature structures located in periapical lesions. Collectively, findings indicate that the evoked-bleeding technique delivers MSCs into the root canal system in mature teeth with apical lesions.

Pulp-Derived Exosomes in a Fibrin-Based Regenerative Root Filling Material

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Clinical efficacy of EDTA ultrasonic activation in the reduction of endotoxins and cultivable bacteria

“…The demineralizing action of EDTA exposes the signalling molecules, and the ultrasonic activation of EDTA enhances this effect (Widbiller et al 2016). Growth factors on the dentine surface can act as chemoattractants and differentiation factors for mesenchymal stem cells from the apical papilla or periapical tissues (Lovelace et al 2011, Chrepa et al 2015.…”

Advanced Scaffolds for Dental Pulp and Periodontal Regeneration

“…59,60 Although the EB strategy has been proposed to treat immature teeth, a recent study also demonstrated the influx of undifferentiated MSCs from the apical region into the pulpal space of mature teeth with apical lesions. 61 …”