Dental Pulp Stem Cells for Salivary Gland Regeneration-Where Are We Today?

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren's syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue.

Socioeconomic disparities between oral cavity cancer patients in Germany.

Objective: In many countries the access to high quality medical service depends on socioeconomic factors. Therefore, these factors are associated with the treatment and prognosis of many diseases. In Germany health care is claimed to be independent from such factors due to obligatory health insurance and a well-developed medical infrastructure. Thus, socioeconomically caused health disparities should be absent. The aim of this study was to analyze the association between socioeconomic factors and the survival of oral cavity cancer in Germany. Patients and methods: In this descriptive cohort study socioeconomic status related factors as well as demographic, tumor-specific, and comorbidity factors of 500 patients treated for oral cavity cancer were obtained in the university hospital of Dresden. Pearson correlation was used to describe associations between continuous variables. Associations between categorical variables were assessed using the chi-square test. Overall and recurrence-free survival were studied using the Kaplan-Meier method. Log-rank test was carried out to test between-group differences. Cox proportional hazard models were used to estimate the risk of death and the risk of recurrence. Results: Significant differences in overall survival were found between the different educational levels and sex. Seventy-nine percent of the patients did not have a university degree or master craftsman/craftswoman. Less discrepancy was observed according to the marital status (49.4% married/engaged vs. 47.8% single, divorced, or widowed). In the multivariable analysis only sex, age at diagnosis, the Charlson score, the number of positive lymph nodes, and the nodal status were identified as independent predictors for overall survival whereas sex and the age at diagnosis were identified as independent predictors for recurrence-free survival. Conclusion: Despite the equitable health system in Germany, significant associations between overall survival of oral cavity cancer and different socioeconomic factors could be found. For elimination of these disparities, health education programs should be established in socially deprived areas. Furthermore, clinicians should keep these factors in mind when determining recall periods for dental check-ups.

Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro.

Tyrosine kinase inhibitors (TKIs), such as imatinib (IMA) and nilotinib (NIL), are the cornerstone of chronic myeloid leukemia (CML) treatment via the blockade of the oncogenic BCR-ABL1 fusion protein. However, skeletal side effects are commonly observed in pediatric patients receiving long-term treatment with IMA. Additionally, in vitro studies have shown that IMA and NIL alter vitamin D metabolism, which may further impair bone metabolism. To determine whether TKIs directly affect bone cell function, the present study treated the human osteoblastic cell line SaOS-2 with IMA or NIL and assessed effects on their mineralization capacity as well as mRNA expression of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), two cytokines that regulate osteoclastogenesis. Both TKIs significantly inhibited mineralization and downregulated osteoblast marker genes, including alkaline phosphatase, osteocalcin, osterix, as well as genes associated with the pro-osteogenic Wnt signaling pathway; NIL was more potent than IMA. In addition, both TKIs increased the RANKL/OPG ratio, which is known to stimulate osteoclastogenesis. The present results suggested that the TKIs IMA and NIL directly inhibited osteoblast differentiation and directly promoted a pro-osteoclastogenic environment through the RANKL-OPG signaling axis. Thus, we propose that future work is required to determine whether the bone health of CML patients undergoing TKI-treatment should be routinely monitored.