Clinical trials using dental stem cells: 2022 update.

For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.

Analysis of Coding RNA and LncRNA Expression Profile of Stem Cells from the Apical Papilla After Depletion of Sirtuin 7.

OBJECTIVE: To explore the effects of Sirtuin 7 (SIRT7) on the gene expression profile of stem cells from the apical papilla (SCAPs). METHODS: SCAPs were isolated and cultured. SIRT7 short hairpin ribonucleic acid (shRNA) was used to knock down the expression of SIRT7 in SCAPs. After library construction and RNA sequencing (RNA-seq), differentially expressed genes were identified using Cuffdiff with a false discovery rate (FDR) ≤ 0.05 and fold change ≥ 2. Pathway and Gene Ontology (GO) analyses were conducted to elucidate the changes in important functions and pathways after SIRT7 gene knockdown. Gene set enrichment analysis (GSEA) was performed and enrichment of a gene set with an FDR lower than 0.25 was considered significant. RESULTS: The most striking GO terms related to SIRT7sh SCAPs and Consh SCAPs were response to nucleus, nucleolus, cytoplasm, protein binding and intrinsic apoptotic signalling pathway. Signalling pathway analysis revealed the top five pathways to be metabolic, pyrimidine metabolism, protein processing in endoplasmic reticulum, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling and p53 signalling. The results of GSEA showed that genes were mainly enriched in cell cycle, cell proliferation, transforming growth factor beta (TGF-ß) signalling and cytokine-cytokine receptor interaction pathways. CONCLUSION: SIRT7 may affect the functions of SCAPs through cell cycle, cell proliferation and apoptosis pathways.

[Increase of saliva nitrate and nitrite level in patients with oral candidiasis].

OBJECTIVE: To observe the alterations of saliva nitrate and nitrite level in patients with oral candidiasis. METHODS: Parotid saliva and whole saliva were collected from 33 patients and 34 healthy volunteers. Concentrations of nitrate and nitrite in saliva were determined by high-performance liquid chromatography. Follow-up observation was performed on 10 patients after treatment. The data were statistically analyzed with independent-samples t test or paired-samples t test at alpha = 0.05. RESULTS: There was significant increase of the concentrations and secretion rate of parotid saliva nitrate in patient group as compared with controls: (49.70 +/- 0.50) vs (21.51 +/- 0.60) mg/L (t = 2.692, P = 0.009) and (27.71 +/- 0.50) vs (12.55 +/- 0.60) microg/min (t = 2.554, P = 0.013), respectively. Significantly increased concentrations and secretion rate of nitrate and nitrite [nitrate: (6.46 +/- 0.94) vs (1.11 +/- 0.70) mg/L (t = 3.792, P = 0.000); nitrite: (8.48 +/- 0.58) vs (3.39 +/- 0.53) mg/L (t = 2.888, P = 0.005); nitrate secretion rate: (10.57 +/- 0.91) vs (2.10 +/- 0.74) microg/min (t = 3.464, P= 0.001); nitrite secretion rate: (13.91 +/- 0.55) vs (6.42 +/- 0.58) microg/min (t = 2.397, P = 0.020)] were revealed in whole saliva of patients group. Significantly decreased nitrate and nitrite levels were also observed in patients after treatment, especially the changes of parotid saliva nitrate secretion rate [(37.50 +/- 0.50) vs (14.34 +/- 0.64) microg/min (t = 3.142, P = 0.012)], whole saliva nitrate [(14.29 +/- 1.01) vs (2.59 +/- 1.03) mg/L (t = 3.475, P = 0.007)] and whole saliva nitrate secretion rate [(25.97 +/- 0.93) vs (4.12 +/- 1.00) microg/min (t = 3.922, P = 0.003)]. CONCLUSION: The present study revealed the significant increase of salivary nitrate and nitrite level in patients with oral candidiasis is considered to be associated with the host defense reaction.

[Alterations of salivary flow rate and oral main pathogens in miniature pig with bilateral parotid gland atrophy].

OBJECTIVE: To observe the effect of bilateral parotid gland atrophy on the whole saliva flow rate and the growth of main oral pathogens in different sites of oral cavity. METHODS: Ten healthy miniature pigs were divided into two groups. The parotid glands of test group (n = 5) were bilaterally ablated by methyl violet. Another healthy five miniature pigs served as the control group. Whole saliva was collected and the whole saliva flow rate detected in both groups at 12 and 24 months respectively after parotid atrophy. The total numbers of oral main pathogens in the first molar, cuspid sub-gingival bacteria plaque and whole saliva were also detected. RESULTS: The whole saliva flow rate was significantly decreased at both 12 and 24 months respectively after atrophy of bilateral parotid gland in miniature pig. Pathogens including Streptococcus mutans, Porphyromonas gingivalis and Fusobacterium nucleatum in different sites oral cavity were increased after bilateral parotid gland atrophy. CONCLUSIONS: Bilateral ablation of the parotid glands led to a significant decrease of whole saliva flow rate. The total numbers of main oral pathogens were increased in different sites of oral cavity.

Antimicrobial effect of acidified nitrate and nitrite on six common oral pathogens in vitro.

BACKGROUND: Salivary nitrate is positively correlated with plasma nitrate and its level is 9 times the plasma level after nitrate loading. Nitrate in saliva is known to be reduced to nitrite by oral bacteria. Nitrate and nitrite levels in saliva are 3 - 5 times those in serum in physiological conditions respectively in our previous study. The biological functions of high salivary nitrate and nitrite are still not well understood. The aim of this in vitro study was to investigate the antimicrobial effects of nitrate and nitrite on main oral pathogens under acidic conditions. METHODS: Six common oral pathogens including Streptococcus mutans NCTC 10449, Lactobacillus acidophilus ATCC 4646, Porphyromonas gingivalis ATCC 33277, Capnocytophaga gingivalis ATCC 33624, Fusobacterium nucleatum ATCC 10953, and Candida albicans ATCC 10231 were cultured in liquid medium. Sodium nitrate or sodium nitrite was added to the medium to final concentrations of 0, 0.5, 1, 2, and 10 mmol/L. All of the microorganisms were incubated for 24 to 48 hours. The optical densities (OD) of cell suspensions were determined and the cultures were transferred to solid nutrient broth medium to observe the minimum inhibitory concentration and minimum bactericidal/fungicidal concentration for the six tested pathogens. RESULTS: Nitrite at concentrations of 0.5 to 10 mmol/L had an inhibitory effect on all tested organisms at low pH values. The antimicrobial effect of nitrite increased with the acidity of the medium. Streptococcus mutans NCTC 10449 was highly sensitive to nitrite at low pH values. Lactobacillus acidophilus ATCC 4646 and Candida albicans ATCC 10231 were relatively resistant to acidified nitrite. Nitrate at the given concentrations and under acidic conditions had no inhibitory effect on the growth of any of the tested pathogens. CONCLUSION: Nitrite, at a concentration equal to that in human saliva, is both cytocidal and cytostatic to six principal oral pathogens in vitro, whereas nitrate at a similar concentration has no antimicrobial effect on these organisms.