N-Cadherin Regulates the Odontogenic Differentiation of Dental Pulp Stem Cells via β-Catenin Activity

Dental pulp stem cell (DPSC) transplantation has shown new prospects in dental pulp regeneration, and is of great significance in the treatment of pulpitis and pulp necrosis. The fate and regenerative potential of stem cells are dependent, to a great extent, on their microenvironment, which is composed of various tissue components, cell populations, and soluble factors. N-cadherin-mediated cell–cell interaction has been implicated as an important factor in controlling the cell-fate commitment of mesenchymal stem cells. In this study, the effect of N-cadherin on odontogenic differentiation of DPSCs and the potential underlying mechanisms, both in vitro and in vivo, was investigated using a cell culture model and a subcutaneous transplantation mouse model. It was found that the expression of N-cadherin was reversely related to the expression of odontogenic markers (dentin sialophosphoprotein, DSPP, and runt-related transcription factor 2, Runx2) during the differentiation process of DPSCs. Specific shRNA-mediated knockdown of N-cadherin expression in DPSCs significantly increased the expression of DSPP and Runx2, alkaline phosphatase (ALP) activity, and the formation of mineralized nodules. Notably, N-cadherin silencing promoted nucleus translocation and accumulation of β-catenin. Inhibition of β-catenin by a specific inhibitor XAV939, reversed the facilitating effects of N-cadherin downregulation on odontogenic differentiation of DPSCs. In addition, knockdown of N-cadherin promoted the formation of odontoblast-like cells and collagenous matrix in β-tricalcium phosphate/DPSCs composites transplanted into mice. In conclusion, N-cadherin acted as a negative regulator via regulating β-catenin activity during odontogenic differentiation of DPSCs. These data may help to guide DPSC behavior by tuning the N-cadherin-mediated cell–cell interactions, with implications for pulp regeneration.

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Simvastatin Induces the Odontogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo

Journal of Endodontics ◽

10.1016/j.joen.2008.11.024 ◽

2009 ◽

Vol 35 (3) ◽

pp. 367-372 ◽

Cited By ~ 53

Author(s):

Yosuke Okamoto ◽

Wataru Sonoyama ◽

Mitsuaki Ono ◽

Kentaro Akiyama ◽

Takuo Fujisawa ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Odontogenic Differentiation ◽

Human Dental Pulp

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Physical and Biological Properties of a Chitosan Hydrogel Scaffold Associated to Photobiomodulation Therapy for Dental Pulp Regeneration: An In Vitro and In Vivo Study

BioMed Research International ◽

10.1155/2021/6684667 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Maria Stella Moreira ◽

Giovanna Sarra ◽

Giovanna Lopes Carvalho ◽

Flavia Gonçalves ◽

Hector Valentin Caballero-Flores ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Energy Density ◽

Dental Pulp ◽

Blood Clot ◽

Chitosan Hydrogel ◽

Pulp Regeneration ◽

Cell Homing

Background. The regeneration of dental pulp, especially in cases of pulp death of immature teeth, is the goal of the regenerative endodontic procedures (REPs) that are based on tissue engineering principles, consisting of stem cells, growth factors, and scaffolds. Photobiomodulation therapy (PBMT) showed to improve dental pulp regeneration through cell homing approaches in preclinical studies and has been proposed as the fourth element of tissue engineering. However, when a blood clot was used as a scaffold in one of these previous studies, only 30% of success was achieved. The authors pointed out the instability of the blood clot as the regeneration shortcoming. Then, to circumvent this problem, a new scaffold was developed to be applied with the blood clot. The hypothesis of the present study was that an experimental injectable chitosan hydrogel would facilitate the three-dimensional spatial organization of endogenous stem cells in dental pulp regeneration with no interference on the positive influence of PBMT. Methods. For the in vitro analysis, stem cells from the apical papilla (SCAPs) were characterized by flow cytometry and applied in the chitosan scaffold for evaluating adhesion, migration, and proliferation. For the in vivo analysis, the chitosan scaffold was applied in a rodent orthotopic dental pulp regeneration model under the influence of PBMT (660 nm; power output of 20 mW, beam area of 0.028 cm2, and energy density of 5 J/cm2). Results. The scaffold tested in this study allowed significantly higher viability, proliferation, and migration of SCAPs in vitro when PBMT was applied, especially with the energy density of 5 J/cm2. These results were in consonance to those of the in vivo data, where pulp-like tissue formation was observed inside the root canal. Conclusion. Chitosan hydrogel when applied with a blood clot and PBMT could in the future improve previous results of dental pulp regeneration through cell homing approaches.

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The Angiogenic Potential of DPSCs and SCAPs in an In Vivo Model of Dental Pulp Regeneration

Stem Cells International ◽

10.1155/2017/2582080 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 23

Author(s):

Petra Hilkens ◽

Annelies Bronckaers ◽

Jessica Ratajczak ◽

Pascal Gervois ◽

Esther Wolfs ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Dental Pulp ◽

In Vivo Model ◽

Angiogenic Growth Factors ◽

Dental Tissue ◽

Pulp Regeneration ◽

3D Printed

Adequate vascularization, a restricting factor for the survival of engineered tissues, is often promoted by the addition of stem cells or the appropriate angiogenic growth factors. In this study, human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAPs) were applied in an in vivo model of dental pulp regeneration in order to compare their regenerative potential and confirm their previously demonstrated paracrine angiogenic properties. 3D-printed hydroxyapatite scaffolds containing DPSCs and/or SCAPs were subcutaneously transplanted into immunocompromised mice. After twelve weeks, histological and ultrastructural analysis demonstrated the regeneration of vascularized pulp-like tissue as well as mineralized tissue formation in all stem cell constructs. Despite the secretion of vascular endothelial growth factor in vitro, the stem cell constructs did not display a higher vascularization rate in comparison to control conditions. Similar results were found after eight weeks, which suggests both osteogenic/odontogenic differentiation of the transplanted stem cells and the promotion of angiogenesis in this particular setting. In conclusion, this is the first study to demonstrate the successful formation of vascularized pulp-like tissue in 3D-printed scaffolds containing dental stem cells, emphasizing the promising role of this approach in dental tissue engineering.

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The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly(l-lactic acid) scaffolds in vitro and in vivo

Acta Biomaterialia ◽

10.1016/j.actbio.2010.04.009 ◽

2010 ◽

Vol 6 (10) ◽

pp. 3856-3863 ◽

Cited By ~ 95

Author(s):

Jing Wang ◽

Xiaohua Liu ◽

Xiaobing Jin ◽

Haiyun Ma ◽

Jiang Hu ◽

...

Keyword(s):

Stem Cells ◽

Lactic Acid ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Odontogenic Differentiation ◽

Human Dental Pulp

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Bone marrow mesenchymal stem cells promote prostate cancer cell stemness via cell–cell contact to activate the Jagged1/Notch1 pathway

Cell & Bioscience ◽

10.1186/s13578-021-00599-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ji-wen Cheng ◽

Li-xia Duan ◽

Yang Yu ◽

Pu Wang ◽

Jia-le Feng ◽

...

Keyword(s):

Prostate Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Western Blot ◽

Cell Contact ◽

Activity Levels ◽

Tumor Resistance ◽

Cell Cell

Abstract Background Mesenchymal stem cells (MSCs) play a crucial role in cancer development and tumor resistance to therapy in prostate cancer, but the influence of MSCs on the stemness potential of PCa cells by cell–cell contact remains unclear. In this study, we investigated the effect of direct contact of PCa cells with MSCs on the stemness of PCa and its mechanisms. Methods First, the flow cytometry, colony formation, and sphere formation were performed to determine the stemness of PCaMSCs, and the expression of stemness-related molecules (Sox2, Oct4, and Nanog) was investigated by western blot analysis. Then, we used western blot and qPCR to determine the activity levels of two candidate pathways and their downstream stemness-associated pathway. Finally, we verified the role of the significantly changed pathway by assessing the key factors in this pathway via in vitro and in vivo experiments. Results We established that MSCs promoted the stemness of PCa cells by cell–cell contact. We here established that the enhanced stemness of PCaMSCs was independent of the CCL5/CCR5 pathway. We also found that PCaMSCs up-regulated the expression of Notch signaling-related genes, and inhibition of Jagged1-Notch1 signaling in PCaMSCs cells significantly inhibited MSCs-induced stemness and tumorigenesis in vitro and in vivo. Conclusions Our results reveal a novel interaction between MSCs and PCa cells in promoting tumorigenesis through activation of the Jagged1/Notch1 pathway, providing a new therapeutic target for the treatment of PCa.

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The effect of fibroblast growth factor 7 on human dental pulp stem cells for differentiation to AQP5 ‐positive and α SMA ‐positive cells in vitro and in vivo

Clinical and Experimental Dental Research ◽

10.1002/cre2.423 ◽

2021 ◽

Author(s):

Yoshihiko Akashi ◽

Atsushi Nemoto ◽

Kei Nakajima ◽

Katsutoshi Kokubun ◽

Satoshi Murakami ◽

...

Keyword(s):

Stem Cells ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Fibroblast Growth ◽

Human Dental Pulp

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P-EP013. Superior migration propensity of dental pulp stem cells in in vitro and in vivo models of excitotoxic neurodegeneration

Clinical Neurophysiology ◽

10.1016/j.clinph.2021.02.176 ◽

2021 ◽

Vol 132 (8) ◽

pp. e82-e83

Author(s):

Sivapriya Senthilkumar ◽

Chaitra Venugopal ◽

K. Shobha ◽

Bindu M. Kutty ◽

Anandh Dhanushkodi

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

In Vivo Models ◽

Migration Propensity

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Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells

Science Advances ◽

10.1126/sciadv.abe3445 ◽

2021 ◽

Vol 7 (5) ◽

pp. eabe3445

Author(s):

Yicun Wang ◽

Jinhui Wu ◽

Hui Chen ◽

Yang Yang ◽

Chengwu Xiao ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Negative Feedback ◽

Direct Interaction ◽

Therapy Resistance ◽

Negative Regulator ◽

Chemotherapy Response ◽

Genome Wide

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

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