Stem cells in dentistry – Part I: Stem cell sources

AbstractStem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties

Therapeutic interactions between mesenchymal stem cells for healing medication-related osteonecrosis of the jaw

Abstract Background Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, including bone marrow, adipose, and mucosa. MSCs have the capacity for self-renewal and differentiation. Reports have been published on the systemic administration of MSCs leading to functional improvements by engraftment and differentiation, thus providing a new strategy to regenerate damaged tissues. Recently, it has become clear that MSCs possess immunomodulatory properties and can therefore be used to treat diseases. However, the therapeutic effect mechanisms of MSCs are yet to be determined. Here, we investigated these mechanisms using a medication-related osteonecrosis of the jaw (MRONJ)-like mouse model. Methods To generate MRONJ-like characteristics, mice received intravenous zoledronate and dexamethasone two times a week. At 1 week after intravenous injection, maxillary first molars were extracted, and at 1 week after tooth extraction, MSCs were isolated from the bone marrow of the mice femurs and tibias. To compare “diseased MSCs” from MRONJ-like mice (d-MSCs) with “control MSCs” from untreated mice (c-MSCs), the isolated MSCs were analyzed by differentiation and colony-forming unit-fibroblast (CFU-F) assays and systemic transplantation of either d-MSCs or c-MSCs into MRONJ-like mice. Furthermore, we observed the exchange of cell contents among d-MSCs and c-MSCs during coculture with all combinations of each MSC type. Results d-MSCs were inferior to c-MSCs in differentiation and CFU-F assays. Moreover, the d-MSC-treated group did not show earlier healing in MRONJ-like mice. In cocultures with any combination, MSC pairs formed cell–cell contacts and exchanged cell contents. Interestingly, the exchange among c-MSCs and d-MSCs was more frequently observed than other pairs, and d-MSCs were distinguishable from c-MSCs. Conclusions The interaction of c-MSCs and d-MSCs, including exchange of cell contents, contributes to the treatment potential of d-MSCs. This cellular behavior might be one therapeutic mechanism used by MSCs for MRONJ.http://deepblue.lib.umich.edu/bitstream/2027.42/134630/1/13287_2016_Article_367.pd

Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Ovariectomy–induced Osteoporotic Phenotype without Causing Osteonecrosis in the Jaw

Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) is a novel bisphosphonate derivative without radioactivity and has been successfully used to treat arthritis in China for years. Since bisphosphonate therapy has the potential to induce bisphosphonate-associated osteonecrosis of the jaw (BRONJ), we examine whether 99Tc-MDP represents a new class of bisphosphonate for anti-resorptive therapy to ameliorate estrogen deficiency–induced bone resorption with less risk of causing BRONJ. We showed that 99Tc-MDP-treated ovariectomized (OVX) mice had significantly improved bone mineral density (BMD) and trabecular bone volume in comparison to the untreated OVX group by inhibiting osteoclasts and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). To determine the potential of inducing BRONJ, 99Tc-MDP/dexamethasone (Dex) or zoledronate/Dex were administered into C57BL/6J mice via the tail vein, followed by extraction of maxillary first molars. Interestingly, 99Tc-MDP treatment showed less risk to induce osteonecrosis in the maxillary bones compared to zoledronate treatment group, partially because 99Tc-MDP neither suppressed adaptive regulatory T cells (Tregs) nor activated the inflammatory T-helper-producing interleukin 17 cells (Th17). Taken together, our findings demonstrate that 99Tc-MDP therapy may be a promising approach in the treatment of osteoporosis with less risk of causing BRONJ

Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Ovariectomy–Induced Osteoporotic Phenotype Without Causing Osteonecrosis in the Jaw

Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) is a novel bisphosphonate derivative without radioactivity and has been successfully used to treat arthritis in China for years. Since bisphosphonate therapy has the potential to induce bisphosphonate-associated osteonecrosis of the jaw (BRONJ), we examine whether 99Tc-MDP represents a new class of bisphosphonate for anti-resorptive therapy to ameliorate estrogen deficiency–induced bone resorption with less risk of causing BRONJ. We showed that 99Tc-MDP-treated ovariectomized (OVX) mice had significantly improved bone mineral density (BMD) and trabecular bone volume in comparison to the untreated OVX group by inhibiting osteoclasts and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). To determine the potential of inducing BRONJ, 99Tc-MDP/dexamethasone (Dex) or zoledronate/Dex were administered into C57BL/6J mice via the tail vein, followed by extraction of maxillary first molars. Interestingly, 99Tc-MDP treatment showed less risk to induce osteonecrosis in the maxillary bones compared to zoledronate treatment group, partially because 99Tc-MDP neither suppressed adaptive regulatory T cells (Tregs) nor activated the inflammatory T-helper-producing interleukin 17 cells (Th17). Taken together, our findings demonstrate that 99Tc-MDP therapy may be a promising approach in the treatment of osteoporosis with less risk of causing BRONJ

Oral Health-Related Quality of Life Changes after Clinical Remounting of Existing Dentures

The clinical remount is an accurate and efficient way to reset the occlusion of delivered removable dentures if major occlusal correction is required. Although previous studies have reported that clinical remounting of existing dentures enhances patients’ oral function, little subjective feedback is available. This retrospective study reports short-term changes in oral-health-related quality of life (OHRQoL) and masticatory function after clinical remounting of existing dentures. Three time points were defined: before adjustment (T0), immediately after adjustment (T1), and 1 week after adjustment (T2). The medical records of seven patients were analyzed. The mean age of participants was 77.71 years, and the mean service period of their prostheses was 9.43 months. The mean scores of the OHIP-EDENT-J questionnaire at the respective time points were 35, 21.14, and 22.14. The mean readings of masticatory function at the respective time points were 76.71, 89.29, and 111.86. Significant differences in the OHIP-EDENT-J were found between T0 and T1, and T0 and T2; and in masticatory function between T1 and T2, and T0 and T2. The results indicated that after rebalancing of the occlusion of the existing dentures, the patient-reported OHRQoL was improved immediately and maintained at least for a short time, and masticatory function was enhanced over a 1-week period

Hypothetical Model of How a Clinical Remount Procedure Benefits Patients with Existing Dentures: A Narrative Literature Review

The clinical remount procedure, which involves remounting the dentures on an articulator with interocclusal records, can effectively reduce occlusal discrepancies. This procedure can be applied not only to new dentures but also to those already in service; however, research in this field is still scarce. This narrative review aims to establish a hypothetical mechanism and possible indications and contraindications for this technique as a basis for further research. Current studies have revealed a high prevalence of malocclusion in delivered dentures. Performing a clinical remount on these existing dentures would enhance the oral function of the denture wearer and would enable effective and accurate correction of the accumulated errors in the jaw relationship in a stable working environment. This technique should be performed if a patient has poor masticatory function or occlusion-related complaints. However, performing a clinical remount on dentures with an excessive anterior–posterior discrepancy between the centric relation and the maximal intercuspal position or on dentures with extremely low occlusal vertical dimension, is considered less effective. The clinical remount procedure remains an essential skill both for fabricating quality dentures and maintaining those already in service

Localization of Integrin Beta-4 Subunit at Soft Tissue–Titanium or Zirconia Interface

Currently, along with titanium (Ti), zirconia is widely used as an abutment material for dental implants because it makes it possible to avoid gingival discoloration; however, the epithelial sealing capability of zirconia remains unknown. The purpose of the present study is to elucidate the localization of integrin β4 subunit (Inβ4), one of the main proteins in the attachment structure between gingival junctional epithelial (JE) cells and substrata. Maxillary first molars were extracted from rats, and implants were placed with Ti or zirconia transgingival parts; then, the localization of Inβ4 was observed. Morphological and functional changes in rat oral epithelial cells (OECs) cultured on a culture dish (Dish) and Ti and zirconia plates were also evaluated with Inβ4 immunofluorescence histochemistry and Western blotting. After four weeks of implant placement, the morphology of the peri-implant epithelium (PIE) and the localization of Inβ4 around the Ti and zirconia transgingival parts were similar. However, both exhibited markedly shorter Inβ4-positive bands in the PIE than in the JE around natural teeth. Decreased expression levels of Inβ4 were observed in OECs cultured on Ti and zirconia plates compared with those cultured on Dish. In conclusion, although inferior to natural teeth, zirconia implants are thought to have epithelial sealing properties comparable to those of titanium

Oral Function Rehabilitation with the Simplified Lauritzen Clinical Remount Technique in a Patient with Bimaxillary Alveolar Exostoses: A Case Report

This case report describes a 70 year-old man with IVA lung cancer who required oral function rehabilitation by fabricating dentures with a simplified clinical remount technique. A pair of dentures were fabricated for a 70-year-old man with stage IVA lung cancer. Due to severe bimaxillary exostoses, the dentures could not properly extend and achieve a peripheral seal. The treatment philosophy was to stabilize the dentures and achieve proper function with optimized occlusion. The simplified Lauritzen clinical remount technique was performed at the time of denture delivery and 3 months later. After the second clinical remount procedure, the patient was able to eat meals with the dentures and maintained in a stable condition. Compared with the original technique, the simplified Lauritzen clinical remount omits the facebow transfer and keeps the condylar guidance setting and the Bennett angle unchanged during the adjustment. The prostheses are mounted to a type 3, non-arcon type articulator with anterior stop screws attached to the bilateral condylar parts. With the aid of anterior stop screws, the eccentric movement of dentures can be differentiated on a millimeter scale and balanced easily. It is effective to use occlusal-optimized dentures and the clinical remount technique, especially in difficult cases

Soft Tissue Interface with Various Kinds of Implant Abutment Materials

Various materials, such as titanium, zirconia and platinum-gold (Pt-Au) alloy, have been utilized for dental implant trans-mucosal parts. However, biological understanding of soft tissue reaction toward these materials is limited. The aim of this study was to compare the response of cell lines and soft tissue to titanium, zirconia and Pt-Au substrata. The surface hydroxyl groups and protein adsorption capacities of the substrata were measured. Next, gingival epithelial-like cells (Sa3) and fibroblastic cells (NIH3T3) were cultured on the materials, and initial cell attachment was measured. Immuno-fluorescent staining of cell adhesion molecules and cytoskeletal proteins was also performed. In the rat model, experimental implants constructed from various materials were inserted into the maxillary tooth extraction socket and the soft tissue was examined histologically and immunohistochemically. No significant differences among the materials were observed regarding the amount of surface hydroxyl groups and protein adsorption capacity. Significantly fewer cells of Sa3 and NIH3T3 adhered to the Pt-Au alloy compared to the other materials. The expression of cell adhesion molecules and a well-developed cytoskeleton was observed, both Sa3 and NIH3T3 on each material. In an animal model, soft tissue with supracrestal tissue attachment was observed around each material. Laminin-5 immuno-reactivity was seen in epithelia on both titanium and zirconia, but only in the bottom of epithelia on Pt-Au alloy. In conclusion, both titanium and zirconia, but not Pt-Au alloy, displayed excellent cell adhesion properties