Treatment with Stem Cells from Human Exfoliated Deciduous Teeth and Their Derived Conditioned Medium Improves Retinal Visual Function and Delays the Degeneration of Photoreceptors.

Retinitis pigmentosa (RP) is a hereditary disease characterized by degeneration and the loss of photoreceptors. Stem cell-based therapy has emerged as a promising strategy for treating RP. Stem cells from exfoliated deciduous teeth (SHEDs), a type of mesenchymal stem cell from human exfoliated deciduous teeth, have the potential to differentiate into photoreceptor-like cells under specific induction in vitro. It has been confirmed that through paracrine secreta, SHEDs exert neurotrophic, angiogenic, immunoregulatory, and antiapoptotic functions in injured tissues. This study was designed to determine whether retinal-differentiated SHEDs and the conditioned medium derived from SHEDs (SHEDs-CM) have therapeutic effects in a mouse model of RP. The results showed that both SHEDs and SHEDs-CM improved electroretinogram responses, ameliorated photoreceptor degeneration, and maintained the structure of the outer segments of photoreceptors. The therapeutic effects were related to antiapoptotic activity of SHEDs and SHEDs-CM. Thus, SHEDs may be a promising stem cell source for treating retinal degeneration.

Teeth-derived stem cells: A source for cell therapy.

Cell therapy is one of the important therapeutic approaches in the treatment of many diseases such as cancer, degenerative diseases, and cardiovascular diseases. Among various cell types, which could be used as cell therapies, stem cell therapy has emerged as powerful tools in the treatment of several diseases. Multipotent stem cells are one of the main classes of stem cells that could originate from different parts of the body such as bone marrow, adipose, placenta, and tooth. Among several types of multipotent stem cells, tooth-derived stem cells (TDSCs) are associated with special properties such as accessible, easy isolation, and low invasive, which have introduced them as a good source for using in the treatment of several diseases such as neural injuries, liver fibrosis, and Cohrn's disease. Here, we provided an overview of TDSCs particular stem cells from human exfoliated deciduous teeth and clinical application of them. Moreover, we highlighted molecular mechanisms involved in the regulation of dental stem cells fate.

Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells.

Cleft lip and palate is the most common congenital anomaly in the orofacial region. Autogenous iliac bone graft, in general, has been employed for closing the bone defect at the alveolar cleft. However, such iliac bone graft provides patients with substantial surgical and psychological invasions. Consequently, development of a less invasive method has been highly anticipated. Stem cells from human exfoliated deciduous teeth (SHED) are a major candidate for playing a significant role in tissue engineering and regenerative medicine. The aim of this study was to elucidate the nature of bone regeneration by SHED as compared to that of human dental pulp stem cells (hDPSCs) and bone marrow mesenchymal stem cells (hBMSCs). The stems cells derived from pulp tissues and bone marrow were transplanted with a polylactic-coglycolic acid barrier membrane as a scaffold, for use in bone regeneration in an artificial bone defect of 4 mm in diameter in the calvaria of immunodeficient mice. Three-dimensional analysis using micro CT and histological evaluation were performed. Degree of bone regeneration with SHED relative to the bone defect was almost equivalent to that with hDPSCs and hBMSCs 12 weeks after transplantation. The ratio of new bone formation relative to the pre-created bone defect was not significantly different among groups with SHED, hDPSCs and hBMSCs. In addition, as a result of histological evaluation, SHED produced the largest osteoid and widely distributed collagen fibers compared to hDPSCs and hBMSCs groups. Thus, SHED transplantation exerted bone regeneration ability sufficient for the repair of bone defect. The present study has demonstrated that SHED is one of the best candidate as a cell source for the reconstruction of alveolar cleft due to the bone regeneration ability with less surgical invasion.

Neuroprotector effect of stem cells from human exfoliated deciduous teeth transplanted after traumatic spinal cord injury involves inhibition of early neuronal apoptosis.

Stem cells from human exfoliated deciduous teeth (SHED) transplants have been investigated as a possible treatment strategy for spinal cord injuries (SCI) due to their potential for promoting functional recovery. The aim of present study was to investigate the effects of SHED on neuronal death after an experimental model of SCI. METHODS: Wistar rats were spinalized using NYU impactor®. Animals were randomly distributed into 4 groups: Control (Naive) or Surgical control, Sham (laminectomy with no SCI); SCI (laminectomy followed by SCI, treated with vehicle); SHED (SCI treated with intraspinal transplantation of 3×105 SHED, 1h after SCI). Functional evaluations and morphological analysis were performed to confirm the spinal injury and the benefit of SHED transplantation on behavior, tissue protection and motor neuron survival. Flow cytometry of neurons, astrocytes, macrophages/microglia and T cells of spinal cord tissue were run at six, twenty-four, forty-eight and seventy-two hours after lesion. Six hours after SCI, ELISA and Western Blot were run to assess pro- and anti-apoptotic factors. The SHED group showed a significant functional improvement in comparison to the SCI animals, as from the first week until the end of the experiment. This behavioral protection was associated with less tissue impairment and greater motor neuron preservation. SHED reduced neuronal loss over time, as well as the overexpression of pro-apoptotic factor TNF-α, while maintained basal levels of the anti-apoptotic BCL-XL six hours after lesion. Data here presented show that SHED transplantation one hour after SCI interferes with the balance between pro- and anti-apoptotic factors and reduces early neuronal apoptosis, what contributes to tissue and motor neuron preservation and hind limbs functional recovery.

Demineralized deciduous tooth as a source of bone graft material: its biological and physicochemical characteristics.

OBJECTIVE: To examine structural and physicochemical characteristics of demineralized deciduous tooth powder (DDTP) in relation to demineralization time and to present potential of using DDTP as a bone graft material. STUDY DESIGN: For structural and physicochemical analysis, scanning electron microscopy, inductively coupled plasma spectrometry, energy-dispersive X-ray analysis, X-ray diffraction analysis, differential scanning calorimetry, and Brunauer-Emmett-Teller surface area analysis were performed. In in vivo experiments, DDTP was grafted in 20 Sprague-Dawley rats' calvarial defects, and radiographic and histologic examination and histomorphometric analysis were performed. RESULTS: In vitro studies confirmed physicochemical demands for collagen-based bone graft material, such as lowered calcium content, lowered crystallinity of hydroxyapatite, and exposed organic structures to demineralization. In vivo experiment indicated new bone formation in DDTP-grafted sites and gradual resorption of the grafted particles. Defect closure rate was significantly higher in the 8-week DDTP-grafted group compared with control (P < .05). CONCLUSIONS: Deciduous teeth had structural and physicochemical characteristics suitable for grafting with appropriate demineralization. Bone healing was observed to have successfully occurred in DDTP-grafted sites.

Stem cells from human exfoliated deciduous tooth-derived conditioned medium enhance recovery of focal cerebral ischemia in rats.

Regenerative therapy using stem cells is a promising approach for the treatment of stroke. Recently, we reported that dental pulp stem cells (DPSC) ameliorated ischemic tissue injury in the rat brain and accelerated functional recovery after middle cerebral artery occlusion (MCAO). In this study, we investigated the effects of stem cells from human exfoliated deciduous tooth (SHED)-derived conditioned medium (SHED-CM) on permanent MCAO (pMCAO). Adult male Sprague-Dawley rats were subjected to pMCAO. SHED-CM were then administered intranasally, and the motor function and infarct volume were evaluated. Neurogenesis and vasculogenesis were determined using immunochemical markers. The SHED-CM group had more positive signals than the Dulbecco's modified Eagle's medium group, with doublecortin (DCX), neurofilament H, neuronal nuclei, and rat endothelial cell antigen observed in the peri-infarct area. Migration of neuronal progenitor cells (NPC) with DCX from the subventricular zone to the peri-infarct area was observed on days 6 and 16, with migration on day 6 being the most prominent. In conclusion, SHED-CM promoted the migration and differentiation of endogenous NPC, induced vasculogenesis, and ameliorated ischemic brain injury after pMCAO as well as transplantation of DPSC.

Transplantation of primary canines after loss or ankylosis of upper permanent incisors. A prospective case series study on healing and survival.

Primary canines were transplanted to replace lost or ankylosed permanent upper incisors. Healing, healing complications and loss and survival were evaluated in a prospective case series study. In total, 27 primary canines were transplanted. Extraorally posts made of titanium were inserted into the root canal from a retrograde direction as an immediate endodontic treatment and as an elongation of the short autologous roots. In some cases antiresorptive-regenerative therapy was used. Inclusion criteria for the evaluation were a minimal observation period of 12 months or the observation of complications. The median observation period of the analyzed 17 transplants was 26.6 months (min: 6.7 months, max: 54.6 months). Sixteen out of seventeen transplants exhibited functional healing until the end of the observation or the occurrence of an external influence (another trauma, resorption by neighbored tooth). In no case ankylosis or arrest of alveolar growth was recorded. In some transplants resorptions not related to infection or ankylosis were observed. One transplant exhibited an early infection-related complication and was removed. One transplant was resorbed by the developing permanent canine and lost. Following another trauma five transplants were lost. External influence and new trauma were significantly related to the loss of transplants (Fisher's exact test; P = 0.0006 and 0.0034). The estimated survival according to a Kaplan-Meier analysis was 40.7 months for all transplants. It was significantly shorter for teeth which were lost in relation to an external influence (survival 28.4 months vs 44.7 months; log rank test: P = 0.0093). The transplantation of primary canines maintains bone and soft tissues of the alveolar process. The healing rate is high. However, there is a high incidence of repeated trauma episodes, causing a high loss rate. The observation period is still limited.

Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

BACKGROUND: The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression. METHODS: Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes. RESULTS AND DISCUSSION: We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent in situ hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age. CONCLUSION: Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches.

Treatment of an avulsed maxillary permanent central incisor by autotransplantation of a primary canine tooth.

AIM: To present a case in which an avulsed permanent maxillary central incisor was replaced by autotransplantation of a primary canine tooth. SUMMARY: The present case describes transplantation of a primary canine tooth into the space left by an avulsed permanent maxillary central incisor after a delay of several days. After root canal treatment, the primary canine tooth was extracted and placed into the prepared socket. To provide better adaptation of the donor tooth, the recipient alveolar site was remodeled using surgical burs. Semi-rigid splinting was maintained for 15 days. The crown of the primary canine was reshaped with composite resin and with an interim prosthesis, preventing movement of the lateral incisor tooth into the space of the transplanted canine. After 24-month follow-up the autotransplanted primary canine showed ankylosis but the tooth was in an acceptable state. The use of permanent tooth autotransplantation has been well documented. However a literature search revealed only one case report on the autotransplantation of primary teeth. KEY LEARNING POINTS: Long term results of primary tooth autotransplantation are scarce but the procedure in this case report could be considered as a temporary space maintainer for the treatment of a patient with a lost permanent incisor under 10 years of age. Success of primary tooth autotransplantation may be affected by several factors, such as case selection, extra oral time, surgical and endodontic procedures.

Influence of aging on tooth eruption: experimental canine mandibular allograft.

PURPOSE: Aging is clinically related to tooth eruption; however, there are no known studies that have elucidated the relationship. We examined whether tooth eruption would occur normally in a mature subject. MATERIALS AND METHODS: Using vascularized composite tissue mandibular transplantation, we extracted portions of immature mandibles including the tooth germs from young beagle dogs and placed them into unrelated immature and mature beagle dogs. We then examined eruption of the lower first molar in the grafted mandibular bone and compared the results clinically, radiographically, and histologically. RESULTS: Normal tooth eruption was observed in the transplanted mandibles in the young dogs. In the mature dogs, eruption from the gingiva was delayed, whereas that from alveolar bone occurred normally in the transplanted mandibles. Further, the whole crown was covered with a cap of gingival tissue in the mature dogs, although this cap was not gingival overgrowth. CONCLUSIONS: Tooth eruption is influenced by some unknown factors related to aging. Apparently, apoptosis did not occur in the connective tissues between the reduced enamel epithelia and oral epithelia that overlay the teeth in the mature subjects.

Auto-alloplastic transplantation of a primary canine after traumatic loss of a permanent central incisor.

This report describes the transplantation of a primary canine after traumatic loss of a central incisor in an 8-year-old boy. The 7-month follow-up revealed normal periodontal healing with absence of infection, ankylosis or progressive resorption. The patient was then lost for control. After 16 months another trauma in the same patient resulted in an avulsion of the transplant. However, the alveolar bone was maintained in vertical and sagittal dimensions. Another primary canine was transplanted and followed for further 11 months. Again normal periodontal healing could be observed. The transplantation of a primary canine is seen as a promising method to replace a lost permanent tooth and maintain the surrounding tissues in very young patients.

Colagem de fragmentos dentários em molares decíduos / Dental reattachment in primary molars

Os autores apresentam uma alternativa para restabelecimento anátomo-funcional de molares decíduos com destruiçäo coronária total. No cumprimento desse objetivo, utilizam coroa dentária total de dentes decíduos, previamente tratados e mantidos em um "banco de dentes", através de colagem no remanescente dentário do paciente pediátrico

Tooth retransplantation among matched and mismatched rhesus monkeys.

Previous reports have suggested that histocompatibility matching increased the survival rate of tooth allografts in humans when transplants were evaluated by clinical and radiographic criteria. In this study, 26 rhesus monkeys were typed and matched for RhLA-A,B antigens, and pairs were subjected to mixed lymphocyte culture (MLC) analysis. Single primary incisor allografts were followed in two months by secondary incisor transplants from the same donors, and all grafts were removed three months later for histologic analysis. All transplants were rejected, and secondary grafts looked like primary grafts even though they had been in place two months less.