Treatment of deep caries with pulpitis is a major challenge in dentistry. Stem cell therapy represents a potential strategy to regenerate the dentin-pulp complex, enabling conservation and restoration of teeth. The objective of this study was to assess the efficacy and safety of pulp stem cell transplantation as a prelude for the impending clinical trials. Clinical-grade pulp stem cells were isolated and expanded according to good manufacturing practice conditions. The absence of contamination, abnormalities/aberrations in karyotype, and tumor formation after transplantation in an immunodeficient mouse ensured excellent quality control. After autologous transplantation of pulp stem cells with granulocyte-colony stimulating factor (G-CSF) in a dog pulpectomized tooth, regenerated pulp tissue including vasculature and innervation completely filled in the root canal, and regenerated dentin was formed in the coronal part and prevented microleakage up to day 180. Transplantation of pulp stem cells with G-CSF yielded a significantly larger amount of regenerated dentin-pulp complex compared with transplantation of G-CSF or stem cells alone. Also noteworthy was the reduction in the number of inflammatory cells and apoptotic cells and the significant increase in neurite outgrowth compared with results without G-CSF. The transplanted stem cells expressed angiogenic/neurotrophic factors. It is significant that G-CSF together with conditioned medium of pulp stem cells stimulated cell migration and neurite outgrowth, prevented cell death, and promoted immunosuppression in vitro. Furthermore, there was no evidence of toxicity or adverse events. In conclusion, the combinatorial trophic effects of pulp stem cells and G-CSF are of immediate utility for pulp/dentin regeneration, demonstrating the prerequisites of safety and efficacy critical for clinical applications. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:521-533
In the first four years of the LHD experiment, several encouraging results have emerged, the most significant of which is that MHD stability and good transport are compatible in the inward shifted axis configuration. The observed energy confinement at this optimal configuration is consistent with ISS95 scaling with an enhancement factor of 1.5. The confinement enhancement over the smaller heliotron devices is attributed to the high edge temperature. We find that the plasma with an average beta of 3% is stable in this configuration, even though the theoretical stability conditions of Mercier modes and pressure driven low-n modes are violated. In the low density discharges heated by NBI and ECR, internal transport barrier (ITB) and an associated high central temperature (>10 keV) are seen. The radial electric field measured in these discharges is positive (electron root) and expected to play a key role in the formation of the ITB. The positive electric field is also found to suppress the ion thermal diffusivity as predicted by neoclassical transport theory. The width of the externally imposed island is found to decrease when the plasma is collisionless with finite beta and increase when the plasma is collisional. The ICRF heating in LHD is successful and a high energy tail (up to 500 keV) has been detected for minority ion heating, demonstrating good confinement of the high energy particles. The magnetic field line structure unique to the heliotron edge configuration is confirmed by measuring the plasma density and temperature profiles on the divertor plate. A long pulse (2 min) discharge with an ICRF power of 0.4 MW has been demonstrated and the energy confinement characteristics are almost the same as those in short pulse discharges.
Recently, mesenchymal stem cells have demonstrated a potential for neurotrophy and neurodifferentiation. We have recently isolated mobilized dental pulp stem cells (MDPSCs) using granulocyte-colony stimulating factor (G-CSF) gradient, which has high neurotrophic/angiogenic potential. The aim of this study is to investigate the effects of MDPSC transplantation on peripheral nerve regeneration. Effects of MDPSC transplantation were examined in a rat sciatic nerve defect model and compared with autografts and control conduits containing collagen scaffold. Effects of conditioned medium of MDPSCs were also evaluated in vitro. Transplantation of MDPSCs in the defect demonstrated regeneration of myelinated fibers, whose axons were significantly higher in density compared with those in autografts and control conduits only. Enhanced revascularization was also observed in the MDPSC transplants. The MDPSCs did not directly differentiate into Schwann cell phenotype; localization of these cells near Schwann cells induced several neurotrophic factors. Immunofluorescence labeling demonstrated reduced apoptosis and increased proliferation in resident Schwann cells in the MDPSC transplant compared with control conduits. These trophic effects of MDPSCs on proliferation, migration, and antiapoptosis in Schwann cells were further elucidated in vitro. The results demonstrate that MDPSCs promote axon regeneration through trophic functions, acting on Schwann cells, and promoting angiogenesis.
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