Efficient bone formation in a swine socket lift model using Escherichia coli-derived recombinant human bone morphogenetic protein-2 adsorbed in ß-tricalcium phosphate.

Several preclinical studies have shown that Escherichia coli-derived bone morphogenetic protein-2 (E-BMP-2) is as effective as mammalian cell-derived bone morphogenetic protein-2 (C-BMP-2) in the treatment of bone defects. However, further investigation of the effectiveness and determination of the optimal dosage of E-BMP-2 in large animals are still necessary before its full application in humans. This study investigated the efficiency of different concentrations of E-BMP-2 adsorbed in ß-TCP for bone augmentation and osseointegration of immediate dental implants in a swine socket lift model. Following exposure of the maxillary sinus lateral wall, a 3.4-mm (diameter) cavity was drilled and filled with 0.1 g of ß-TCP containing different doses of E-BMP-2 (0, 10, 30, or 100 µg/site) to lift the Schneiderian membrane. A dental implant was then immediately inserted. Bone-to-implant contact (BIC) and bone density (BD) examined via histological analysis were used as parameters to assess E-BMP-2 efficiency in bone formation. The implant stability quotient (ISQ) was measured using Osstell to determine the effect of E-BMP-2/ß-TCP on implant stability. After 8 weeks, the groups that received 30 and 100 µg of E-BMP-2 showed substantial new bone formation in the elevated space, while no bone formation was observed with ß-TCP alone. Accordingly, BIC and BD presented a dose-dependent response to increasing doses of E-BMP-2. However, there was no increase in implant stability with E-BMP-2 treatment. In conclusion, the E-BMP-2/ß-TCP combination was efficient in bone formation and osseointegration of dental implants in a socket lift model in mini-pigs.

Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.

The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.

Regeneration of calvarial defects with Escherichia coli -derived rhBMP-2 adsorbed in PLGA membrane.

OBJECTIVE: Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) has been shown to be as effective as mammalian cell-derived BMP-2. However, several in vitro and in vivo experiments are still necessary to validate the effectiveness of E-BMP-2 due to the difference in synthesis process, mainly related to protein nonglycosylation. The objective of this study was to investigate whether biodegradable polylactide-co-glycolide (PLGA) membrane is a suitable carrier for E-BMP-2 delivery for bone regeneration of critical-sized defects in rat calvaria. MATERIALS AND METHODS: First, the osteoinductive effect of E-BMP-2 was confirmed in vitro in mouse bone marrow stromal cells by analysis of osteocalcin mRNA levels, and calcium deposition was detected by alizarin red staining. Before in vivo experiments, the release profile of E-BMP-2 from PLGA membranes was determined by ELISA. E-BMP-2 (0, 1, 5 and 10 µg/µl) was applied for ectopic and orthotopic bone formation and was analyzed by X-ray, micro-CT and histology. RESULTS: Release-profile testing showed that PLGA membrane could retain 94% of the initially applied E-BMP-2. Ectopic bone formation assay revealed that combination of E-BMP-2/PLGA membrane strongly induced bone formation. Stronger osteoinductivity with complete repair of critical-sized defects was observed only with PLGA membranes adsorbed with 5 and 10 µg/µl of E-BMP-2, whereas no bone formation was observed in the groups that received no membrane or 0-µg/µl dose of E-BMP-2. CONCLUSION: PLGA membrane was shown to be a suitable carrier for sustained release of E-BMP-2, and the E-BMP-2/PLGA membrane combination was demonstrated to be efficient in bone regeneration in a model of critical-sized defects.

White discharge formation following a subepithelial connective tissue graft for anterior fixed partial denture pontics: A case report based on clinical and histological findings.

PATIENT: A 54-year-old woman presenting with anterior alveolar ridge resorption was submitted to a connective tissue graft (CTG) for esthetic improvement before rehabilitation with a fixed partial denture. Palate-harvested connective tissue was used as a graft after extra-oral removal of the epithelium. Unexpectedly, complete wound healing was not observed. Moreover, 6 months post-surgery, a white discharge was detected at the grafted site. The adjacent tooth showing a root fracture was initially associated with the symptoms and was then extracted. Concomitantly, the unhealed tissue at the grafted site was also excised, leading to temporary symptom resolution. However, the white discharge reappeared after 2 months. The excision area was expanded to remove the grafted tissue entirely, and the wound was completely healed. Since the alveolar ridge resorption had become larger compared to the preoperative condition, the patient was subjected to a second CTG, now using a connective tissue harvested from the palate by a single incision technique. The wound healed uneventfully, and the final prosthesis was delivered 6 months after soft tissue stabilization. The patient has been followed-up for more than 28 months without any recurrence of white discharge. DISCUSSION: Histopathological and cytological examination detected keratinized epithelial tissues and cells, respectively, in excised tissues and white discharge specimens. Consequently, a possible relationship between white discharge and residual epithelium in the harvested graft was strongly suspected. CONCLUSION: Success of the CTG procedure requires careful method selection for tissue transplantation and treatment execution.

Mesenchymal stem cell-mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice.

Subcutaneous transplants of bone marrow mesenchymal stem cells (BMMSCs) are capable of generating ectopic bone and organizing functional hematopoietic marrow elements in animal models. Here we report that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate as a carrier suppressed age-related degeneration in multiple organs and benefited an increase in life span extension compared with control littermates. The newly organized ectopic bone/marrow system restores active hematopoiesis via the erythropoietin receptor/signal transducer and activator of transcription 5 (Stat5) pathway. Furthermore, the BMMSC recipient mice showed elevated level of Klotho and suppression of insulin-like growth factor I signaling, which may be the mechanism contributing to the alleviation of aging-like phenotypes and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hematopoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice.

Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2.

Multiple roles have been already recognized for CCN2 in cartilage development and regeneration. However, the effects of CCN2 on bone regeneration remain to be elucidated. In this study, the utility of CCN2 on bone regeneration was examined in vitro and in vivo in combination with hydroxyapatite (HAp) as a scaffold. Human bone marrow stromal cells (hBMSCs) were isolated from human iliac bone marrow aspirates of healthy donors and expanded, and the effects of CCN2 on their proliferation and migration were examined in vitro. The proliferation of hBMSCs on a plastic or HAp plate was significantly enhanced by CCN2. Moreover, the migration of hBMSCs also dramatically increased by CCN2. Interestingly, a C-terminal signal modular fragment of CCN2 (CT-module) also enhanced the cell proliferation and migration as efficiently as the full-length CCN2. Next, in order to estimate the effect of CCN2 on the migration and survival of hBMSCs and bone formation inside the HAp scaffold in vivo, two experiments were performed. First, the porous HAp carrier was cultured with hBMSCs for a week, and the cell-scaffold hybrid was transplanted with or without CCN2 subcutaneously into immunocompromised mice. CCN2 accelerated the hBMSC-like cell migration and survival inside the porous HAp within 4 weeks after transplantation. Second, the porous HAp carrier with or without CCN2 was directly implanted into bone defects within a rabbit mandible, and bone regeneration inside was evaluated. As a result, CCN2 efficiently induced the cell invasion and bone formation inside the porous HAp scaffold. These findings suggest that CCN2 and its CT-module fragment could be useful for regeneration and reconstruction of large-scale bone defects.

Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study.

Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells or DPSCs) and deciduous teeth (stem cells from human exfoliated deciduous teeth). We recently discovered another type of MSCs in the apical papilla of human immature permanent teeth termed stem cells from the apical papilla (SCAP). Here, we further characterized the apical papilla tissue and stem cell properties of SCAP using histologic, immunohistochemical, and immunocytofluorescent analyses. We found that the apical papilla is distinctive to the pulp in terms of containing less cellular and vascular components than those in the pulp. Cells in the apical papilla proliferated 2- to 3-fold greater than those in the pulp in organ cultures. Both SCAP and DPSCs were as potent in osteo/dentinogenic differentiation as MSCs from bone marrows, whereas they were weaker in adipogenic potential. The immunophenotype of SCAP is similar to that of DPSCs on the osteo/dentinogenic and growth factor receptor gene profiles. Double-staining experiments showed that STRO-1 coexpressed with dentinogenic markers such as bone sialophosphoprotein, osteocalcin, and growth factors FGFR1 and TGFbetaRI in cultured SCAP. Additionally, SCAP express a wide variety of neurogenic markers such as nestin and neurofilament M upon stimulation with a neurogenic medium. We conclude that SCAP are similar to DPSCs but a distinct source of potent dental stem/progenitor cells. Their implications in root development and apexogenesis are discussed.

Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model.

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine.

A longitudinal retrospective study of the analysis of the risk factors of implant failure by the application of generalized estimating equations.

PURPOSE: Many studies have identified risk factors for dental implant failure, although few have investigated the correlation among implant fixtures within single patients. A better analytical method may include repeated measures analysis including generalized estimating equations (GEE). This retrospective cohort study aimed to (1) identify the risk factors for failure of dental implantation and (2) evaluate an analytical method using GEE analysis. METHODS: We analyzed data on early and late implant failures in 296 patients providing 721 rough surface dental implants (2.44 implants per patient). Potential predictors of implant failure included age, gender, smoking, location of implant, use of bone augmentation, number of remaining teeth, opposing tooth condition, fixture length, fixture diameter and type of suprastructure (fixed or removable partial denture). The likelihood of early and late implant failure was estimated by GEE. RESULTS: The early failure rate was 1.5% (11/721 implants, 7/296 patients) and the 10-year cumulative survival rate was 94.0% (7/710 implants, 5/293 patients). The GEE analysis revealed that a significant risk factor for early implant failure was smoking (p<0.01), whereas significant risk factors for late failure were maxillary implant (p=0.02), posterior implant (p<0.01), number of remaining teeth (≥20) (p<0.01), opposing unit being a removable partial denture or nothing (p=0.04) and having a removable type suprastructure (p<0.01). CONCLUSIONS: GEE analysis showed that smoking was a risk factor for early implant failure, and several risk factors were identified for late implant failure.

Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-ß3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration.

Articular cartilage repair remains a challenging problem. Based on a high-throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF-ß3) strongly potentiated chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF-ß3-treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF-ß3-induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates the mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to the glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed that the mTORC1/AKT pathway and the glucocorticoid receptor was highly activated with FA and TA, but to a lesser extent with DEX. Collectively, these results show a unique ability of FA to enhance TGF-ß3-associated chondrogenesis, and suggest that the FA/TGF-ß3 combination may be used as major inducer of chondrogenesis in vitro. Additionally, FA/TGF-ß3 could be potentially applied in a clinical setting to increase the efficiency of regenerative approaches based on chondrogenic differentiation of stem cells.

In silico comparison of the reproducibility of full-arch implant provisional restorations to final restoration between a 3D Scan/CAD/CAM technique and the conventional method.

PURPOSE: The aim of this article was to investigate the accuracy in the reproducibility of full-arch implant provisional restorations to final restorations between a 3D Scan/CAD/CAM technique and the conventional method. METHODS: We fabricated two final restorations for rehabilitation of maxillary and mandibular complete edentulous area and performed a computer-based comparative analysis of the accuracy in the reproducibility of the provisional restoration to final restoration between a 3D scanning and CAD/CAM (Scan/CAD/CAM) technique and the conventional silicone-mold transfer technique. Final restorations fabricated either by the conventional or Scan/CAD/CAM method were successfully installed in the patient. The total concave/convex volume discrepancy observed with the Scan/CAD/CAM technique was 503.50mm(3) and 338.15 mm(3) for maxillary and mandibular implant-supported prostheses (ISPs), respectively. On the other hand, total concave/convex volume discrepancy observed with the conventional method was markedly high (1106.84 mm(3) and 771.23 mm(3) for maxillary and mandibular ISPs, respectively). CONCLUSIONS: The results of the present report suggest that Scan/CAD/CAM method enables a more precise and accurate transfer of provisional restorations to final restorations compared to the conventional method.

The BMP2 antagonist inhibitor L51P enhances the osteogenic potential of BMP2 by simultaneous and delayed synergism.

Bone morphogenetic protein 2 (BMP2) is a potent osteoinductive cytokine that plays crucial roles in bone repair. However, large amounts of BMP2 are required to induce sufficient bone formation in humans possibly due to a feedback response of BMP antagonists. The engineered BMP2 variant L51P is deficient in BMP receptor type I activation but maintains affinity for BMP antagonists and can allow for the inactivation of BMP antagonists, and eventually enhance BMP2 action. As hypothesized, simultaneous addition of L51P enhanced the BMP2-induced osteogenesis. To test the ability of L51P to competitively inactivate BMP antagonists, cell binding affinity of BMP2 ligands was investigated in the presence or absence of L51P. Because the BMP antagonists were highly expressed 3 days after exogenous BMP2 stimulation, we collected supernatants from 3-day stimulated cell cultures and used as condition culture media (CM). The results showed a significant decrease in the cell binding of BMP2 ligands when cells were incubated with exogenous BMP2 and CM, whereas L51P addition competitively rescued the suppression of BMP2-to-cell binding induced by CM incubation. In a delayed experimental model, L51P was applied 3 days after exogenous BMP2 stimulation and we could observe a striking enhancement of the BMP2-induced SMAD-1/5/8 phosphorylation and luciferase activity of the Id1 promoter compared to the simultaneous addition of the two factors. These findings provide a deeper insight into the cellular and molecular mechanisms involved in the effect of L51P in suppressing the BMP antagonists and enhancing BMP activity. Additionally, these results demonstrate that L51P is a promising down regulator of BMP-induced negative feedback, which could have a significant impact in future applications of BMP2 in research and clinical settings.

A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells.

INTRODUCTION: During normal pulp tissue healing, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) or interleukins, act in the initial 48 hours (inflammatory phase) and play important roles not only as chemo-attractants of inflammatory cells and stem/progenitor cells but also in inducing a cascade of reactions toward tissue regeneration or reparative dentin formation or both. Previous reports have shown that inflammatory cytokines regulate the differentiation capacity of dental pulp stem/progenitor cells (DPCs), but none has interrogated the impact of these cytokines on the stem cell phenotype of stem/progenitor cells. This study investigated the effects of a short-term treatment with TNF-α on the stem cell phenotype and differentiation ability of human DPCs. METHODS: An in vivo mouse model of pulp exposure was performed for analysis of expression of the mesenchymal stem cell marker CD146 in DPCs during the initial stage of inflammatory response. For in vitro studies, human DPCs were isolated and incubated with TNF-α for 2 days and passaged to eliminate TNF-α completely. Analysis of stem cell phenotype was performed by quantification of cells positive for mesenchymal stem cell markers SSEA-4 (stage-specific embryonic antigen 4) and CD146 by flow cytometry as well as by quantitative analysis of telomerase activity and mRNA levels of OCT-4 and NANOG. Cell migration, colony-forming ability, and differentiation toward odontogenesis and adipogenesis were also investigated. RESULTS: The pulp exposure model revealed a strong staining for CD146 during the initial inflammatory response, at 2 days after pulp exposure. In vitro experiments demonstrated that a short-term (2-day) treatment of TNF-α increased by twofold the percentage of SSEA-4+ cells. Accordingly, STRO-1, CD146, and SSEA-4 protein levels as well as OCT-4 and NANOG mRNA levels were also significantly upregulated upon TNF-α treatment. A short-term TNF-α treatment also enhanced DPC function, including the ability to form cell colonies, to migrate, and to differentiate into odontogenic and adipogenic lineages. CONCLUSIONS: A short-term treatment with TNF-α enhanced the stem cell phenotype, migration, and differentiation ability of DPCs.

Novel chondrogenic and chondroprotective effects of the natural compound harmine.

A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the ß-carboline alkaloid harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2α1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine was shown to ameliorate TNFα-induced decrease in expression of CCN2 and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation.

A retrospective comparative 8-year study of cumulative complications in teeth adjacent to both natural and implant-supported fixed partial dentures.

PURPOSE: To compare the complication rate of natural teeth adjacent to implant supported dentures (IFDs) with that of teeth serving as abutments for fixed partial dentures (FPDs). The second goal was to assess the risk factors for complications in teeth adjacent to bounded edentulous spaces. MATERIALS AND METHODS: The study subjects were selected from patients who received prosthodontic treatment for their bounded edentulous space not exceeding two missing teeth between February 1990 and March 2007. Sixty-one patients were included in the IFD group and 66 patients were included in the FPD group. Tooth complications were defined as tooth extraction, periodontal lesion, periapical lesion, and loss of prosthesis and were assessed by one examiner based on dental records. RESULTS: The 8-year cumulative complication rate for the IFD group (7.9%) was significantly lower than for the FPD group (40.7%). Additionally, the 8-year cumulative complication rate of vital teeth (6%) was significantly lower than that of nonvital teeth (45.9%). A cox proportional hazard analysis revealed that nonvitality of dental pulp was a significant risk factor for tooth complications, whereas treatment modality was not. CONCLUSIONS: Teeth adjacent to IFD-treated edentulous spaces presented fewer complications than natural teeth serving as abutments for FPDs. Conservation of teeth adjacent to edentulous spaces as vital teeth was the key finding to limit further tooth loss.

miRNA-720 controls stem cell phenotype, proliferation and differentiation of human dental pulp cells.

Dental pulp cells (DPCs) are known to be enriched in stem/progenitor cells but not well characterized yet. Small non-coding microRNAs (miRNAs) have been identified to control protein translation, mRNA stability and transcription, and have been reported to play important roles in stem cell biology, related to cell reprogramming, maintenance of stemness and regulation of cell differentiation. In order to characterize dental pulp stem/progenitor cells and its mechanism of differentiation, we herein sorted stem-cell-enriched side population (SP) cells from human DPCs and periodontal ligament cells (PDLCs), and performed a locked nucleic acid (LNA)-based miRNA array. As a result, miR-720 was highly expressed in the differentiated main population (MP) cells compared to that in SP cells. In silico analysis and a reporter assay showed that miR-720 targets the stem cell marker NANOG, indicating that miR-720 could promote differentiation of dental pulp stem/progenitor cells by repressing NANOG. Indeed, gain-and loss-of-function analyses showed that miR-720 controls NANOG transcript and protein levels. Moreover, transfection of miR-720 significantly decreased the number of cells positive for the early stem cell marker SSEA-4. Concomitantly, mRNA levels of DNA methyltransferases (DNMTs), which are known to play crucial factors during stem cell differentiation, were also increased by miR-720 through unknown mechanism. Finally, miR-720 decreased DPC proliferation as determined by immunocytochemical analysis against ki-67, and promoted odontogenic differentiation as demonstrated by alizarin red staining, as well as alkaline phosphatase and osteopontin mRNA levels. Our findings identify miR-720 as a novel miRNA regulating the differentiation of DPCs.

Retrospective comparative ten-year study of cumulative survival rates of remaining teeth in large edentulism treated with implant-supported fixed partial dentures or removable partial dentures.

PURPOSE: This study aimed to compare the survival rates of remaining teeth between implant-supported fixed dentures (IFDs) and removable partial dentures (RPDs) in patients with large edentulous cases. The second goal was to assess the risk factors for remaining tooth loss. MATERIALS AND METHODS: The study subjects were selected among those who received prosthodontic treatment at Okayama University Dental Hospital for their edentulous space exceeding at least four continuous missing teeth. Twenty-one patients were included in the IFD group and 82 patients were included in the RPD group. Survival rates of remaining teeth were calculated in three subcategories: (1) whole remaining teeth, (2) adjacent teeth to intended edentulous space, and (3) opposing teeth to intended edentulous space. RESULTS: The ten-year cumulative survival rate of the whole remaining teeth was significantly higher in the IFD group (40.0%) than in the RPD group (24.4%). On the other hand, there was no significant difference between two groups in the survival rate of teeth adjacent or opposing to intended edentulous space. A Cox proportional hazard analysis revealed that RPD restoration and gender (male) were the significant risk factors for remaining tooth loss (whole remaining teeth). CONCLUSIONS: These results suggest that IFD treatment can reduce the incidence of remaining tooth loss in large edentulous cases.

Retrospective investigation of the remaining teeth status of patients with implant-supported fixed partial dentures in unilateral free-end edentulism.

PURPOSE: This study aimed to compare the various complication-free rates and survival rates of remaining teeth among implant-supported fixed dentures (IFDs), removable partial dentures (RPDs) and no-restoration (NR) patients with unilateral free-end edentulism. MATERIAL AND METHODS: The study subjects were selected among those who received prosthodontic treatment at Okayama University Dental Hospital for their unilateral free-end edentulism (2 or 3 missing teeth). Thirty-three patients were included in the IFD group, 41 matched patients in the RPD group, and 10 patients who received RPDs but refused their use were regarded as NR group. The remaining dentition was classified into five subcategories in relation to the missing portion: adjacent teeth to the missing portion (AD), contralateral posterior dentition in the same jaw (CS) and in the opposite jaw (CO), ipsilateral opposing posterior dentition (IO), and anterior dentition (AN). Complications were defined as tooth extraction, periodontal lesions, periapical lesions or loss of retention of the prosthesis and were assessed by one examiner based on the hospital chart records. RESULTS: The cumulative complication-free rates in the remaining teeth were significantly different among each of the three groups (p<0.01), with a significantly lower incidence rate in the IFD group. Regarding the cumulative survival rate of the remaining teeth, there was a significant difference only between IFD and NR group (p=0.01), especially in the CO region (p=0.04). CONCLUSIONS: Stable posterior occlusal support obtained with IFD treatment for unilateral free-end edentulism may reduce the incidence of complications in the remaining teeth, by decreasing the adverse mechanical stress.

Stem cells in dentistry--Part II: Clinical applications.

New technologies that facilitate solid alveolar ridge augmentation are receiving considerable attention in the field of prosthodontics because of the growing requirement for esthetic and functional reconstruction by dental implant treatments. Recently, several studies have demonstrated potential advantages for stem-cell-based therapies in regenerative treatments. Mesenchymal stem/stromal cells (MSCs) are now an excellent candidate for tissue replacement therapies, and tissue engineering approaches and chair-side cellular grafting approaches using autologous MSCs represent the clinical state of the art for stem-cell-based alveolar bone regeneration. Basic studies have revealed that crosstalk between implanted donor cells and recipient immune cells plays a key role in determining clinical success that may involve the recently observed immunomodulatory properties of MSCs. Part II of this review first overviews progress in regenerative dentistry to consider the implications of the stem cell technology in dentistry and then highlights cutting-edge stem-cell-based alveolar bone regenerative therapies. Factors that affect stem-cell-based bone regeneration as related to the local immune response are then discussed. Additionally, pre-clinical stem cell studies for the regeneration of teeth and other oral organs as well as possible applications of MSC-based immunotherapy in dentistry are outlined. Finally, the marketing of stem cell technology in dental stem cell banks with a view toward future regenerative therapies is introduced.

Stem cells in dentistry--part I: stem cell sources.

Stem 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.