Regenerative application of oral and maxillofacial 3D organoids based on dental pulp stem cell.

Dental pulp stem cells (DPSCs) originate from the neural crest and the present mesenchymal phenotype showed self-renewal capabilities and can differentiate into at least three lineages. DPSCs are easily isolated with minimal harm, no notable ethical constraints, and without general anesthesia to the donor individuals. Furthermore, cryopreservation of DPSCs provides this opportunity for autologous transplantation in future studies without fundamental changes in stemness, viability, proliferation, and differentiating features. Current approaches for pulp tissue regeneration include pulp revascularization, cell-homing-based regenerative endodontic treatment (RET), cell-transplantation-based regenerative endodontic treatment, and allogeneic transplantation. In recent years, a novel technology, organoid, provides a mimic physiological condition and tissue construct that can be applied for tissue engineering, genetic manipulation, disease modeling, single-cell high throughput analysis, living biobank, cryopreserving and maintaining cells, and therapeutic approaches based on personalized medicine. The organoids can be a reliable preclinical prediction model for evaluating cell behavior, monitoring drug response or resistance, and comparing healthy and pathological conditions for therapeutic and prognostic approaches. In the current review, we focused on the promising application of 3D organoid technology based on DPSCs in oral and maxillofacial tissue regeneration. We discussed encountering challenges and limitations, and found promising solutions to overcome obstacles.

Histologic and Histomorphometric Comparative Study of Oral Lichen Planus Versus Oral Lichenoid Reaction.

Aim: Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease classified as an oral potentially malignant disorder (OPMD) and increased transformation risk to oral cancer. Oral lichenoid reactions (OLRs) share the clinical manifestations of OLP. This study aimed to determine histomorphometric changes in OLPs and OLRs in comparison to the healthy control, which helps to plan for the establishment of diagnostic criteria. Materials and Methods: This cross-sectional prospective study was conducted on a total of 75 tissue-embedded paraffin-block samples, including OLPs (n = 25), OLR cases (n = 25), and healthy control individuals (n = 25). The study groups were compared by chi-squared, Fisher's exact, and one-way ANOVA tests. A p-value less than 0.05 was considered statistically significant. Results: Comparison of the nuclear area and cellular area showed a statistically significant difference between study groups in basal and parabasal layer (P < 0.05). Comparison of the nuclear-to-cytoplasm ratio showed a statistically significant difference between study groups in basal (P < 0.05) but not in the parabasal region (P = 0.681). Conclusion: We showed a significant difference in the nuclear and cellular area, nuclear-to-cytoplasm ratio between OLPs and OLRs, and healthy controls, but there was no statistically significant difference between OLPs and OLRs. Thus, these parameters cannot be applied to differentiate diagnoses between OLPs and OLRs.

Association between Vitamin D Receptor Polymorphism and Susceptibility to Oral Lichen Planus and Oral Squamous Cell Carcinoma.

Introduction: Oral squamous cell carcinomas (OSCC) comprise 90-95% of oral cancers. Early diagnosis improved the survival rate of OSCC patients to 80-90%. Oral lichen planus (OLP) is a chorionic inflammatory disease with malignancy potential. The vitamin D receptor (VDR) plays a critical role in the pathogenesis of oral cancer. This study aimed to determine the association between VDR rs7975232 (Apa I) polymorphism and potential susceptibility to OLP and OSCC risks. Materials and Methods: In this prospective case-control study, a total of 120 blood samples were obtained from OSCC patients (n=29), OLP (n=50), and controls (n=40). VDR rs7975232 polymorphism was studied using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistical analysis was performed with SPSS Version 23 software. Data were expressed as means ± standard deviation (SD). Age, sex, allelic frequency, and genotyping were compared using the chi-square test. A p-value of less than 0.05 was regarded as statistically significant. The disease risk was estimated by Odds ratio (OR) with a 95% confidence interval. Results: A significant age difference was observed between the controls and the OSCC group (p=0.001). A significant difference was observed in Aa and aa genotypes compared with AA between OSCCs and controls. Moreover, dominant (p<0.001), additive (p<0.001), and allelic (p=0.001) models were different between groups. Conclusion: There was a positive association between rs7975232 VDR polymorphism and susceptibility to OSCC. More experimental evidence must reveal the possible association between rs7975232 and the risk of OLP in a larger cohort.

Prognostic value of CD44 expression in oral squamous cell carcinoma: A meta-analysis.

CD44 as a marker of cancer stem cells (CSCs) may be correlated with tumor growth, cell migration, metastasis and chemo-radiotherapy resistance of cancers. However, the prognostic value of CD44 in oral squamous cell carcinoma(OSCC) remains controversial. Therefore, the purpose of the current study was to evaluate the correlation of CD44 expression with the prognosis of OSCC through a meta-analysis. We systematically searched PubMed, Scopus, ISI Web of Science, Embase and Cochrane Central databases for relevant studies up to November 2022. We included 11 articles with immunohistochemistry (IHC) method involving 1084 OSCC patients. Hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were calculated to assess the association between CD44 expression and overall survival (OS) and disease-free survival (DFS). Results showed that high expression of CD44 was a poor prognostic marker for OS in OSCC patients (HR: 1.71, 95 % CI: 1.18-2.47). Also results for DFS demonstrated that in patients with high CD44 expression who received treatment, the probability of tumor recurrence or death was 1.66 times and in the worst case this ratio can reach 2.39 (HR: 1.66, 95 % CI: 1.15-2.39). High CD44 expression associated with metastasis to lymph nodes and distant metastasis, poorer survival of the patients, tumor recurrence, higher tumor stage and grade and aggressive clinicopathological features. Therefore CD44 can be used as a valuable independent marker in predicting the prognosis of OSCC patients.

Evaluation of Tenascin Expression in Ameloblastoma, Odontogenic Keratocyst, and Dentigerous Cyst by Immunohistochemistry.

Background: The aim of this study was to evaluate the expression pattern of tenascin in ameloblastoma, odontogenic keratocyst, and dentigerous cyst. Materials and Methods: The expression of tenascin was evaluated in microscopic slides of 42 paraffin blocks including 12 ameloblastomas, 15 odontogenic keratocysts, and 15 dentigerous cysts by immunohistochemistry. The expression of tenascin was examined in stroma, epithelium-connective tissue interface, and epithelium of the lesions by two pathologists semiquantitatively. Results: Stromal expression of tenascin was higher in ameloblastomas than other groups. All the paired groups showed significant differences except comparison of odontogenic keratocysts and dentigerous cysts. Epithelial-mesenchymal interface expression of tenascin was significantly higher in ameloblastomas and odontogenic keratocysts than dentigerous cysts. All the paired groups showed significant differences except comparison of odontogenic keratocysts and ameloblastomas. Expression of tenascin in epithelial cells of ameloblastomas was focal whereas in odontogenic keratocysts and dentigerous cysts negative immunoreactivity was reported. Conclusions: Expression of tenascin in these lesions suggests that it could play a role in epithelial-mesenchymal interaction. Higher expression of tenascin in ameloblastoma, can explain immaturity of its stroma and aggressive nature of this lesion compared with other studied groups. Moreover, higher expression of tenascin in epithelial-mesenchymal interface of odontogenic keratocyst compared with dentigerous cyst reveals its more immature and aggressive nature and high rate of recurrence.

Osteosarcoma of the mandible: A case with a clinical appearance similar to benign lesions.

A 34-year-old woman with complaints of mandibular swelling that started 4 months earlier was referred to the Oral Diseases Department. Based on the clinical and radiographic appearance, the primary diagnosis was an intraosseous reactive lesion. However, the result of histopathology indicated osteosarcoma.

Evaluation of CD24 and CD44 as cancer stem cell markers in squamous cell carcinoma and epithelial dysplasia of the oral cavity by q- RT-PCR.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common cancer of the oral cavity and may be preceded by dysplastic epithelial lesion. Oral SCC (OSCC) contains a rare subset of cancer cells with self-renewal ability, termed as cancer stem cells (CSCs). CD24 and CD44 as CSC markers are cell surface glycoproteins. These markers contribute to the onset, maintenance, and extension of tumor growth, as well as angiogenesis. In the present study, these two markers were simultaneously evaluated to provide a specific phenotype for carcinogenesis process in oral cavity. MATERIALS AND METHODS: In this analytical-cross-sectional study, the expression of CD24 and CD44 genes was evaluated in 45 OSCCs (20 low-grade and 25 high-grade) and 15 oral epithelial dysplasia specimens by real-time quantitative reverse transcription polymerase chain reaction. Kruskal-Wallis and Mann-Whitney U-test, Kendall, and Spearman tests were used for statistical analysis. The significance level was considered <0.05. RESULTS: High expression of both markers genes was reported in two-thirds of samples. There was no significant difference between studied groups in gene expression of CD24 and CD44 whereas statistically significant association between CD24 and CD44 was observed in all three groups. This correlation was more significant in OSCC groups (P < 0.001). CONCLUSION: High expression of CSC markers in OSCC and oral epithelial dysplasia revealed the importance of accurate examination of dysplastic lesions with high expression of these markers and the possibility of malignant transformation. Regarding a significant association of two markers, further studies are necessary to provide a specific phenotype (CD44 high CD24 high) for these lesions.