scholarly journals C5L2 Regulates DMP1 Expression during Odontoblastic Differentiation

2019 ◽  
Vol 98 (5) ◽  
pp. 597-604 ◽  
Author(s):  
F. Chmilewsky ◽  
R. Liang ◽  
M. Kanazawa ◽  
I. About ◽  
L.F. Cooper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Matrix Protein ◽  
Dental Pulp Stem Cells ◽  
Negative Regulator ◽  
Immunofluorescent Staining ◽  
Stem Cell Markers ◽  
C5a Receptor ◽  
Pulp Regeneration ◽  
Odontoblastic Differentiation

The presence of stem cells within the dental-pulp tissue as well as their differentiation into a new generation of functional odontoblast-like cells constitutes an important step of the dentin-pulp regeneration. Recent investigations demonstrated that the complement system activation participates in 2 critical steps of dentin-pulp regeneration: pulp progenitor’s recruitment and pulp nerve sprouting. Surprisingly, its implication in odontoblastic differentiation has not been addressed yet. Since the complement receptor C5a receptor-like 2 (C5L2) is expressed by different stem cells, the aim of this study is to investigate if the dental pulp stem cells express C5L2 and if this receptor participates in odontoblastic differentiation. Immunohistochemistry performed on human third molar pulp sections showed a perivascular co-localization of the mesenchymal stem cell markers STRO1 and C5L2. In vitro immunofluorescent staining confirmed that hDPSCs express C5L2. Furthermore, we determined by real-time polymerase chain reaction that the expression of C5L2 is highly modulated in human dental pulp stem cells (hDPSCs) undergoing odontoblastic differentiation. Moreover, we showed that this odontogenesis-regulated expression of C5L2 is specifically potentiated by the proinflammatory cytokine TNFα. Using a C5L2-siRNA silencing strategy, we provide direct evidence that C5L2 constitutes a negative regulator of the dentinogenic marker DMP1 (dentin matrix protein 1) expression by hDPSCs. Our findings suggest a direct correlation between the odontoblastic differentiation and the level of C5L2 expression in hDPSCs and identify C5L2 as a negative regulator of DMP1 expression by hDPSCs during the odontoblastic differentiation and inflammation processes. This work is the first to demonstrate the involvement of C5L2 in the biological function of stem cells, provides an important knowledge in understanding odontoblastic differentiation of dental pulp stem cells, and may be useful in future dentin-pulp engineering strategies.

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.

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 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.

scholarly journals Odontoblast-Like Cells Differentiated from Dental Pulp Stem Cells Retain Their Phenotype after Subcultivation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Paula A. Baldión ◽  
Myriam L. Velandia-Romero ◽  
Jaime E. Castellanos
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Matrix Protein ◽  
Dental Materials ◽  
Dental Pulp Stem Cells ◽  
Cell Physiology ◽  
Pulp Tissue ◽  
Alizarin Red ◽  
Dentin Matrix Protein ◽  
Mineral Deposition

Odontoblasts, the main cell type in teeth pulp tissue, are not cultivable and they are responsible for the first line of response after dental restauration. Studies on dental materials cytotoxicity and odontoblast cells physiology require large quantity of homogenous cells retaining most of the phenotype characteristics. Odontoblast-like cells (OLC) were differentiated from human dental pulp stem cells using differentiation medium (containing TGF-β1), and OLC expanded after trypsinization (EXP-21) were evaluated and compared. Despite a slower cell growth curve, EXP-21 cells express similarly the odontoblast markers dentinal sialophosphoprotein and dentin matrix protein-1 concomitantly with RUNX2 transcripts and low alkaline phosphatase activity as expected. Both OLC and EXP-21 cells showed similar mineral deposition activity evidenced by alizarin red and von Kossa staining. These results pointed out minor changes in phenotype of subcultured EXP-21 regarding the primarily differentiated OLC, making the subcultivation of these cells a useful strategy to obtain odontoblasts for biocompatibility or cell physiology studies in dentistry.

scholarly journals Odontoblastic differentiation of dental pulp stem cells from healthy and carious teeth on an original PCL-based 3D scaffold

2017 ◽  
Vol 51 ◽  
pp. e252-e263 ◽  
Author(s):  
A. Louvrier ◽  
E. Euvrard ◽  
L. Nicod ◽  
G. Rolin ◽  
F. Gindraux ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
3D Scaffold ◽  
Odontoblastic Differentiation ◽  
Carious Teeth

scholarly journals Cell-derived micro-environment helps dental pulp stem cells promote dental pulp regeneration

2017 ◽  
Vol 50 (5) ◽  
pp. e12361 ◽  
Author(s):  
Xuexin Zhang ◽  
Hui Li ◽  
Jingjing Sun ◽  
Xiangyou Luo ◽  
Hefeng Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Pulp Regeneration

Dental Pulp Stem Cells in Pulp Regeneration

2021 ◽  
Vol 02 (03) ◽  
Author(s):  
Saberian E ◽  
Jalili Sadrabad M ◽  
Petrasova A ◽  
Izadi A
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Pulp Regeneration

scholarly journals The Interplay of Dental Pulp Stem Cells and Endothelial Cells in an Injectable Peptide Hydrogel on Angiogenesis and Pulp Regeneration In Vivo

2015 ◽  
Vol 21 (3-4) ◽  
pp. 550-563 ◽  
Author(s):  
Waruna Lakmal Dissanayaka ◽  
Kenneth M. Hargreaves ◽  
Lijian Jin ◽  
Lakshman P. Samaranayake ◽  
Chengfei Zhang
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Pulp Regeneration ◽  
Peptide Hydrogel

scholarly journals Dental pulp stem cells: Potential significance in regenerative medicine

2008 ◽  
Vol 55 (3) ◽  
pp. 170-179 ◽  
Author(s):  
Vera Todorovic ◽  
Dejan Markovic ◽  
Nadezda Milosevic-Jovcic ◽  
Marijana Petakov ◽  
Bela Balint ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Matrix Protein ◽  
Dental Pulp Stem Cells ◽  
Deciduous Teeth ◽  
High Plasticity ◽  
Dental Stem Cells ◽  
Periodontal Tissues ◽  
Extracellular Matrix Components

To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.

Sign in / Sign up

Export Citation Format

Share Document