Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice.

BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5-10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) administration has been shown to ameliorate muscle weakness in the experimental autoimmune myasthenia gravis (EAMG) model induced by AChR immunization. METHODS: To investigate the efficacy of stem cell treatment in MuSK-related EAMG, clinical and immunological features of MuSK-immunized mice with or without dental follicle MSC (DFMSC) treatment were compared. RESULTS: MuSK-immunized mice intravenously treated with DFMSC after second and third immunizations showed significantly lower EAMG incidence and severity and reduced serum anti-MuSK antibody, NMJ IgG, and C3 deposit levels and CD11b+ lymph node cell ratios. Moreover, lymph node cells of DFMSC-administered mice showed reduced proliferation and IL-6 and IL-12 production responses to MuSK stimulation. By contrast, proportions of B and T cell populations and production of a wide variety of cytokines were not affected from DFMSC treatment. CONCLUSIONS: Our results suggest that DFMSC treatment shows its beneficial effects mostly through suppression of innate immune system, whereas other immune functions appear to be preserved. Stem cell treatment might thus constitute a specific and effective treatment method in MuSK-associated MG.

Immunomodulatory properties and in vivo osteogenesis of human dental stem cells from fresh and cryopreserved dental follicles.

In our previous study, dental follicle tissues from extracted wisdom teeth were successfully cryopreserved for use as a source of stem cells. The goals of the present study were to investigate the immunomodulatory properties of stem cells from fresh and cryopreserved dental follicles (fDFCs and cDFCs, respectively) and to analyze in vivo osteogenesis after transplantation of these DFCs into experimental animals. Third passage fDFCs and cDFCs showed similar expression levels of interferon-γ receptor (CD119) and major histocompatibility complex class I and II (MHC I and MHC II, respectively), with high levels of CD119 and MHC I and nearly no expression of MHC II. Both fresh and cryopreserved human DFCs (hDFCs) were in vivo transplanted along with a demineralized bone matrix scaffold into mandibular defects in miniature pigs and subcutaneous tissues of mice. Radiological and histological evaluations of in vivo osteogenesis in hDFC-transplanted sites revealed significantly enhanced new bone formation activities compared with those in scaffold-only implanted control sites. Interestingly, at 8 weeks post-hDFC transplantation, the newly generated bones were overgrown compared to the original size of the mandibular defects, and strong expression of osteocalcin and vascular endothelial growth factor were detected in the hDFCs-transplanted tissues of both animals. Immunohistochemical analysis of CD3, CD4, and CD8 in the ectopic bone formation sites of mice showed significantly decreased CD4 expression in DFCs-implanted tissues compared with those in control sites. These findings indicate that hDFCs possess immunomodulatory properties that involved inhibition of the adaptive immune response mediated by CD4 and MHC II, which highlights the usefulness of hDFCs in tissue engineering. In particular, long-term preserved dental follicles could serve as an excellent autologous or allogenic stem cell source for bone tissue regeneration as well as a valuable therapeutic agent for immune diseases.

Survival and success rates of autotransplanted premolars: a prospective study of the protocol for developing teeth.

INTRODUCTION: The aim of this prospective clinical trial was to examine the predictability of the protocol for premolar transplantation when applied by an inexperienced surgeon. Additional objectives were to examine the hard and soft tissues and to compare the findings with control premolars and also to record the patients' opinions of the treatment provided. METHODS: The sample comprised 23 consecutively transplanted developing premolars in 19 patients. Their mean age at surgery was 12 years 8 months (range, 9 years 10 months-17 years). The mean observation time was 35 months (range, 6-78 months). Plaque accumulation, pocket depth, gingival recession, mobility, and pulp sensitivity were recorded for the transplanted and the control teeth. Standardized radiographs were used to examine hard tissues and crown-to-root ratios. Questionnaires were used to register each patient's opinion about the treatment and its outcome. RESULTS: The survival rate was 100%, and the success rate was 91.3%. No significant differences were recorded between transplanted and control teeth. The patients' perceptions of the surgical management and the treatment outcome were favorable. CONCLUSIONS: The protocol for autotransplantation of developing premolars in growing patients was successfully adopted, regardless of lack of previous experience with this type of treatment.

Human neural crest-derived postnatal cells exhibit remarkable embryonic attributes either in vitro or in vivo.

During human embryonic development, odontogenic tissues, deriving from the neural crest, remain undifferentiated until the adult age. This study was aimed at characterising the cells of the follicle enveloping the dental germ, due to its direct origin from neural crests. Sixty dental follicles were collected from patients aged 18 to 45 years. This research has clarified that dental follicles, if extracted in a very early stage, when dental roots did not start to be formed, contain a lineage of cells, characterised by a high degree of plasticity in comparison with other adult stem cell populations. In particular, we found that these cells share the following features with ES: (i) high levels of embryonic stem cell markers (CD90, TRA1-60, TRA1-81, OCT-4, CD133, and SSEA-4); (ii) mRNA transcripts for Nanog and Rex-1; (iii) broader potency, being able to differentiate in cell types of all three germ layer, including smooth and skeletal muscle, osteoblasts, neurons, glial cells, and adipocytes; (iv) high levels of telomerase activity; (v) ability to form embryoid bodies; (vi) ability, after injection in murine blastocysts, to be localised within the inner cell mass; (vii) no teratoma formation after injection; (viii) in vivo tissue formation after transplantation. Our results demonstrate that these cells represent a very easy accessible and extraordinary source of pluripotent cells and point out the fact that they own the cardinal feature of embryonic stem cells.

Tooth autotransplantation in orthodontic patients.

AIM: The aims of this report are to present three cases of autotransplantation along with a review of the indications, selection criteria for patient donor and recipient sites, and the major steps in the surgical procedure. BACKGROUND: Autogenous tooth transplantation, or autotransplantation, is the surgical movement of a tooth from one location in the mouth to another in the same individual. It can be a good treatment option in many cases if the dentist knows the implications, indications, and contraindications. CASE DESCRIPTIONS: Three cases with different treatment indications and plans are presented. All showed autotransplantation of teeth as part of orthodontic treatment. It emphasized the benefits of this treatment modality such as new bone formation and lower costs. One case, a rare example of multiple congenitally missing teeth treated by autotransplantation, also was presented. SUMMARY: As shown in these case reports, there are instances where the autotransplantation of teeth is appropriate and may possibly simplify future planned orthodontic or prosthodontic treatment. CLINICAL SIGNIFICANCE: Tooth autotransplantation is an easy and good treatment option, applicable in a lot of cases, substituting different types of prostheses, including dental implants.

Evidence for expansion-based temporal BMP4/NOGGIN interactions in specifying periodontium morphogenesis.

Dental follicle cells in the periodontium are known to have the ability to differentiate into fibroblasts, cementoblasts, and osteoblasts during mouse periodontal development. From embryonic day 14 (E14) to postnatal day 11 (PN11), histological observations showed dramatic alterations in the relative width of the periodontal ligament (PDL)-forming region between the alveolar bone-forming and tooth root-forming area. At PN2, the width of the PDL-forming region showed a minimum, but with a higher expression of NOGGIN and proliferation cell nuclear antigen than the other regions. At PN11, the relative width of the PDL-forming region had expanded. Transplantation of individual regions of the developing tooth germ under the kidney renal capsule showed that dental follicle cells at E14 possessed the potential to develop into mineralized tissue after 3 weeks. These results suggested that the recovery of PDL width at PN11 may have resulted from cell proliferation and molecular interactions between osteogenic factors and their antagonists, such as interactions between bone morphogenetic protein 4 (BMP4) and NOGGIN, simlilar to those observed in suture, limb, and somite formation. To confirm the molecular interaction between BMP4 and NOGGIN, NOGGIN-protein bead implantation onto cultures was employed in vitro. This study thus indicates that harmonious interactions between NOGGIN and BMP in PDL-forming cells, which show higher cell proliferation than neighboring cells, might be important for proper periodontium development.

Creation of a chimaeric periodontium in the rat by isotopic tooth germ transplantation.

The purpose of this work was to develop and test a chimaeric periodontium in which it would be possible to distinguish between connective tissue cells of odontogenic and oral mucosal origin. The recombinant periodontium was created by transplanting first maxillary molar tooth germs with their follicles from 1-3-day-old hooded Lister rats into the corresponding evacuated crypts of 6-9-day-old histocompatible recipients of the same strain. Of 71 transplants, 22 had formed erupted teeth 3 weeks later, with dentogingival junctions and periodontal ligaments histologically similar to those of control teeth. The recombinant nature of the graft periodontium was confirmed by incubating tooth germs in vitro with tritiated thymidine before grafting them, and then demonstrating radiolabelled nuclei in the dentogingival junctions formed by the transplants. Labelled cells were randomly distributed within the periodontal ligament and predominantly near to the basement membrane of junctional epithelium.