Schwann Cell-Derived EVs Facilitate Dental Pulp Regeneration through Endogenous Stem Cell Recruitment via SDF-1/CXCR4 Axis

2021 ◽  
Author(s):  
Dianri Wang ◽  
Yun Lyu ◽  
Yan Yang ◽  
Sicheng Zhang ◽  
Guoqing Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Schwann Cell ◽  
Dental Pulp ◽  
Pulp Regeneration ◽  
Cell Recruitment ◽  
Cxcr4 Axis ◽  
Endogenous Stem Cell

scholarly journals A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4357
Author(s):  
Sahng G. Kim
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Scoping Review ◽  
Clinical Studies ◽  
Dental Pulp ◽  
Animal Studies ◽  
Risk Of Bias ◽  
Pulp Regeneration

Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.

Simvastatin Promotes Dental Pulp Stem Cell–induced Coronal Pulp Regeneration in Pulpotomized Teeth

2016 ◽  
Vol 42 (7) ◽  
pp. 1049-1054 ◽  
Author(s):  
Weiqian Jia ◽  
Yuming Zhao ◽  
Jie Yang ◽  
Wenjun Wang ◽  
Xu Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Dental Pulp ◽  
Pulp Regeneration ◽  
Dental Pulp Stem Cell

scholarly journals Characterization of Stable Hypoxia-Preconditioned Dental Pulp Stem Cells: Implication for Pulp Regeneration

2020 ◽  
Author(s):  
Mohammed Zayed ◽  
Koichiro Iohara ◽  
Hideto Watanabe ◽  
Mami Ishikawa ◽  
Michiyo Tominaga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
Clinical Utility ◽  
Dental Pulp Stem Cells ◽  
Proliferation Rate ◽  
Stem Cell Marker ◽  
Stem Cell Markers ◽  
Pulp Tissue ◽  
Pulp Regeneration

Abstract 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. Our clinical study has demonstrated safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. It is well known that the oxygen concentration is closely linked to the maintenance of stemness. Thus, in this investigation, hypoxia-preconditioned DPSCs (hpDPSCs) was characterized to develop and improve the clinical utility for regeneration of dental pulp in endodontics.Methods: Colony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ were investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of blood and urine. tests Results: hpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly up-regulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation Conclusions: These results demonstrated that hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

Preliminary Study on Dental Pulp Stem Cell–mediated Pulp Regeneration in Canine Immature Permanent Teeth

2013 ◽  
Vol 39 (2) ◽  
pp. 195-201 ◽  
Author(s):  
Yuanyuan Wang ◽  
Yuming Zhao ◽  
Weiqian Jia ◽  
Jie Yang ◽  
Lihong Ge
Keyword(s):  
Stem Cell ◽  
Dental Pulp ◽  
Permanent Teeth ◽  
Pulp Regeneration ◽  
Dental Pulp Stem Cell ◽  
Preliminary Study

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

2021 ◽  
Author(s):  
Mohammed Zayed ◽  
Koichiro Iohara ◽  
Hideto Watanabe ◽  
Mami Ishikawa ◽  
Michiyo Tominaga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
Clinical Utility ◽  
Dental Pulp Stem Cells ◽  
Proliferation Rate ◽  
Stem Cell Marker ◽  
Stem Cell Markers ◽  
Pulp Regeneration ◽  
Potential Clinical Utility

Abstract 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. However, The device for isolation of MDPSCs, however, is not cost effective and requires prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSCs proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry.Methods: Colony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ were investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of blood and urine tests. Results: hpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly up-regulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation. Conclusions: These results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

scholarly journals Pulp Stem Cell–Mediated Functional Pulp Regeneration

2018 ◽  
Vol 98 (1) ◽  
pp. 27-35 ◽  
Author(s):  
B. Sui ◽  
C. Chen ◽  
X. Kou ◽  
B. Li ◽  
K. Xuan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
De Novo ◽  
Convincing Evidence ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Pulp Regeneration ◽  
Regenerative Endodontics

The preservation of vital dental pulp with vasculature and nerve components remains one of the most significant challenges in modern dentistry. Due to the immense potential for neurovascularization, mesenchymal stem cell (MSC) transplantation has shown emerging promise in regenerative medicine and dental translational practice. Actually, pulp mesenchymal stem cells, including postnatal dental pulp stem cells (from permanent teeth) and stem cells from human exfoliated deciduous teeth, possess unique properties based on their origins from neural crest or glial cells. Furthermore, they reside in a neurovascular niche and have the potential for neurogenesis, angiogenesis, and neurovascular inductive activity. According to current pulp regeneration strategies, pulp stem cell–mediated approaches to regeneration have demonstrated convincing evidence that they can rebuild the complex histologic structure of native pulp in situ with highly organized physiologic patterns or even achieve de novo regeneration of complete dental pulp tissues. More importantly, recent clinical studies emphasized in situ neurovascularization outcomes in successful regeneration of vitalized pulp via pulp stem cell transplantation. In this review, we summarize recent breakthroughs in pulp stem cell–mediated pulp regeneration, emphasizing the crucial achievement of neurovascularization. This functional pulp regeneration represents an innovative and promising approach for future regenerative endodontics.

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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mohammed Zayed ◽  
Koichiro Iohara ◽  
Hideto Watanabe ◽  
Mami Ishikawa ◽  
Michiyo Tominaga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
Clinical Utility ◽  
Dental Pulp Stem Cells ◽  
Proliferation Rate ◽  
Stem Cell Marker ◽  
Stem Cell Markers ◽  
Pulp Regeneration ◽  
Potential Clinical Utility

Abstract 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. The device for isolation of MDPSCs, however, is not cost-effective and requires a prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSC proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry. Methods Colony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity, and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ was investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of the blood and urine tests. Results hpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration, and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly upregulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation. Conclusions These results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

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