Dental Pulp Regeneration in Dogs Using a CCR3 Antagonist Without Transplantation of Dental Pulp Stem Cells.

Introduction: Our previous study showed that transplantation of dental pulp stem cells (DPSCs) in combination with a chemokine receptor 3 (CCR3) antagonist into the root canals of aged dogs promoted dental pulp regeneration. In this study, we attempted to regenerate dental pulp in young dogs using a CCR3 antagonist without DPSC transplantation.

Methods: The teeth of dogs were histologically evaluated 4 weeks after extraction of the pulp and administration of scaffold materials and CCR3 antagonist (KDH-136) into the root canal.

Periostin Is a Candidate Regulator of the Host Microenvironment in Regeneration of Pulp and Dentin Complex and Periodontal Ligament in Transplantation with Stem Cell-Conditioned Medium.

Purpose: The microenvironment is required for tissues to maintain their properties . This microenvironment encompasses the types and three-dimensional arrangement of cells forming the tissues, and their interactions with neighboring cells and extracellular matrices, as represented by the stem cell niche. Tissue regeneration depends not on the original tissue source of the transplanted cells, but on the microenvironment in which they are transplanted.

Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs.

Background: Application of pulp regenerative cell therapy for mature teeth with periapical lesions is a critical clinical challenge. The bacterial infection in inaccessible location within the root canal system and in the periapical lesions could cause resistance and impediment, leading to limitations in successful therapy. Thus, the aim of this study was to examine the effect of residual bacteria on the outcome of pulp regeneration in mature teeth with apical periodontitis in dogs.

Biological characteristics and pulp regeneration potential of stem cells from canine deciduous teeth compared with those of permanent teeth.

Background: Clinical studies have demonstrated that dental pulp stem cells isolated from permanent teeth (PT-DPSCs) are safe and efficacious for complete pulp regeneration in mature pulpectomized permanent teeth with complete apical closure. Moreover, dental pulp stem cells from deciduous teeth (DT-DPSCs) have also been shown to be useful for pulp regenerative cell therapy of injured immature permanent teeth. However, direct comparisons of the pulp regenerative potential of DT-DPSCs and PT-DPSCs from the same individual have not been performed.

Pulp Regenerative Cell Therapy for Mature Molars: A Report of 2 Cases.

Regenerative cell therapy using autologous dental pulp stem cells (DPSCs) in mature single-rooted teeth is a potential alternative to traditional endodontic treatment. However, there is no evidence supporting the use of DPSCs in multirooted teeth. This case report aimed to demonstrate the feasibility and outcomes of pulp regenerative cell therapy in mature multirooted molars, which typically have a higher prevalence of apical deltas.

Age Related Senescence, Apoptosis, and Inflammation Profiles in Periodontal Ligament Cells from Canine Teeth.

Objective: The periapical tissues, including periodontal ligament cells (PDLCs) play an important role in repairing the surrounding tissue of the teeth. A decrease in the regenerative potentiality of resident stem cells (PDLCs) has been suggested to be attributed to the decline of pulp regeneration. Therefore, examining the functional changes in periodontal tissue and cells that occur during the aging process is necessary.

Characterization of stable hypoxia-preconditioned dental pulp stem cells compared with mobilized dental pulp stem cells for application for pulp regenerative therapy.

Background: Dental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. We have demonstrated the safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration.

Effects of -Cresol on Senescence, Survival, Inflammation, and Odontoblast Differentiation in Canine Dental Pulp Stem Cells.

Aging, defined by a decrease in the physical and functional integrity of the tissues, leads to age-associated degenerative diseases. There is a relation between aged dental pulp and the senescence of dental pulp stem cells (DPSCs). Therefore, it is important to investigate the molecular processes underlying the senescence of DPSCs to elucidate the dental pulp aging mechanisms.

Pulp Regeneration: Current Approaches, Challenges, and Novel Rejuvenating Strategies for an Aging Population.

We showed the safety and efficacy of pulp regenerative therapy by the autologous transplantation of mobilized dental pulp stem cells with granulocyte colony-stimulating factor in a pilot clinical study of young and middle-aged pulpectomized teeth. An experimental study in dogs further demonstrated an age-dependent decline in the amount of regenerated pulp tissue. In our society, in which people will soon live beyond 100 years, this therapy should be efficacious for contributing to the functional survival and endurance of the tooth not only for pulpectomized young teeth but also for aged teeth with periapical disease.

Treatment of Pulpectomized Teeth With Trypsin Prior to Transplantation of Mobilized Dental Pulp Stem Cells Enhances Pulp Regeneration in Aged Dogs.

There is an age-dependent decline of pulp regeneration, due to the decline of migration, proliferation, and cell survival of resident stem cells. Trypsin is a proteolytic enzyme clinically used for tissue repair. Here, we investigated the effects of trypsin pretreatment of pulpectomized teeth prior to cell transplantation on pulp regeneration in aged dogs.

Immunomodulation and Regeneration Properties of Dental Pulp Stem Cells: A Potential Therapy to Treat Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic, originating from Wuhan, China, is known to cause severe acute respiratory symptoms. The occurrence of a cytokine storm in the lungs is a critical step in the disease pathogenesis, as it causes pathological lesions, pulmonary edema, and acute respiratory distress syndrome, potentially resulting in death. Currently, there is no effective treatment that targets the cytokine storm and helps regenerate the damaged tissue.

Nanobubble-Enhanced Antimicrobial Agents: A Promising Approach for Regenerative Endodontics.

Introduction: In this study, we investigated the properties of nanobubble (NB) water and its effect on smear layer removal and strengthening the efficiency of disinfecting agents used in regenerative endodontic treatment.

Methods: NB water was generated in a NB Generator. The NB size, concentration, and pH were measured.

CCR3 antagonist protects against induced cellular senescence and promotes rejuvenation in periodontal ligament cells for stimulating pulp regeneration in the aged dog.

Pulp regeneration after transplantation of mobilized dental pulp stem cells (MDPSCs) declines in the aged dogs due in part to the chronic inflammation and/or cellular senescence. Eotaxin-1/C-C motif chemokine 11 (CCL11) is an inflammation marker via chemokine receptor 3 (CCR3). Moreover, CCR3 antagonist (CCR3A) can inhibit CCL11 binding to CCR3 and prevent CCL11/CCR3 signaling.

Magnetic resonance imaging in endodontics: a literature review.

Objectives: Magnetic resonance imaging (MRI) has recently been used for the evaluation of dental pulp anatomy, vitality, and regeneration. This study reviewed the recent use of MRI in the endodontic field.

Methods: Literature published from January 2000 to March 2017 was searched in PubMed using the following Medical Subject Heading (MeSH) terms: (1) MRI and (dental pulp anatomy or endodontic pulp); (2) MRI and dental pulp regeneration.

Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications.

Animal models are essential for tissue regeneration studies. This review summarizes and discusses the small and large animal models, including mouse, ferret, dog, and miniswine that have been utilized to experiment and to demonstrate stem cell-mediated dental pulp tissue regeneration. We describe the models based on the location where the tissue regeneration is tested-either ectopic, semiorthotopic, or orthotopic.

Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration.

Background: We recently demonstrated that autologous transplantation of mobilized dental pulp stem cells (MDPSCs) was a safe and efficacious potential therapy for total pulp regeneration in a clinical study. The autologous MDPSCs, however, have some limitations to overcome, such as limited availability of discarded teeth from older patients. In the present study, we investigated whether MDPSCs can be used for allogeneic applications to expand their therapeutic use.

Recent Progress in Translation from Bench to a Pilot Clinical Study on Total Pulp Regeneration.

Based on a preclinical bench study in dogs, a pilot clinical study was completed. Dental pulp stem cell (DPSC) subsets were isolated by mobilization by granulocyte colony-stimulating factor and expanded in good manufacturing practice conditions. The safety and efficacy of their autologous transplantation for total pulp regeneration was assessed in 5 patients with irreversible pulpitis.

Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study.

Background: Experiments have previously demonstrated the therapeutic potential of mobilized dental pulp stem cells (MDPSCs) for complete pulp regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in pulpectomized teeth.

Methods: Five patients with irreversible pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation.

Assessment of Pulp Regeneration Induced by Stem Cell Therapy by Magnetic Resonance Imaging.

Introduction: This study was designed to evaluate the usefulness of magnetic resonance imaging (MRI) to assess the regeneration of pulp tissue.

Methods: Mobilized dental pulp stem cells and granulocyte colony-stimulating factor with collagen were transplanted into mature pulpectomized teeth for pulp regeneration (n = 4). The controls consisted of pulpectomized teeth with or without collagen and normal teeth with intact pulp tissue (n = 4, each).

Trophic Effects of Dental Pulp Stem Cells on Schwann Cells in Peripheral Nerve Regeneration.

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.

Trophic Effects and Regenerative Potential of Mobilized Mesenchymal Stem Cells From Bone Marrow and Adipose Tissue as Alternative Cell Sources for Pulp/Dentin Regeneration.

Dental pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete pulp regeneration. The supply of autologous pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy.

Mechanical forces induce odontoblastic differentiation of mesenchymal stem cells on three-dimensional biomimetic scaffolds.

The mechanical induction of cell differentiation is well known. However, the effect of mechanical compression on odontoblastic differentiation remains to be elucidated. Thus, we first determined the optimal conditions for the induction of human dental pulp stem cells (hDPSCs) into odontoblastic differentiation in response to mechanical compression of three-dimensional (3D) scaffolds with dentinal tubule-like pores.

Isolation of a stable subpopulation of mobilized dental pulp stem cells (MDPSCs) with high proliferation, migration, and regeneration potential is independent of age.

Insights into the understanding of the influence of the age of MSCs on their cellular responses and regenerative potential are critical for stem cell therapy in the clinic. We have isolated dental pulp stem cells (DPSCs) subsets based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs) from young and aged donors. The aged MDPSCs were efficiently enriched in stem cells, expressing high levels of trophic factors with high proliferation, migration and anti-apoptotic effects compared to young MDPSCs.

Mobilized dental pulp stem cells for pulp regeneration: initiation of clinical trial.

Stem cell therapy is a potential strategy to regenerate the dentin-pulp complex, enabling the conservation and restoration of functional teeth. We assessed the efficacy and safety of pulp stem cell transplantation as a prelude before the initiation of clinical trials. Granulocyte-colony stimulating factor (G-CSF) induces subsets of dental pulp stem cells to form mobilized dental pulp stem cells (MDPSCs).