scholarly journals SHED Aggregate Derived Exosomes-shuttled miR-222 Promotes the Regenerative Properties of Periodontal Ligament Stem Cells

2021 ◽  
Author(s):  
Feng Zhou ◽  
Jia Guo ◽  
Fang Wang ◽  
Wanmin Zhao ◽  
Xiaoning He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Defect ◽  
Periodontal Ligament ◽  
Underlying Mechanism ◽  
Tube Formation ◽  
Deciduous Teeth ◽  
Aggregate Formation ◽  
Periodontal Ligament Stem Cells ◽  
Mirna Sequencing

Abstract Background: Periodontal ligament stem cells (PDLSCs) aggregate is still limited in clinical application for lack of angiogenesis. This study aimed to investigate the effects and underlying mechanism of exosomes derived from stem cells from human exfoliated deciduous teeth (SHED) aggregate (SA-Exo) on the aggregate formation and angiogenic properties of PDLSCs.Methods: SA-Exo were isolated by ultracentrifugation. The effect of SA-Exo on the aggregate formation and angiogenic differentiation of PDLSCs were evaluated by investigating extracellular matrix (ECM) deposition and tube formation assay. MicroRNA (miRNA) sequencing was employed to screen different miRNA expression. The effect of targeting miRNA on ECM deposition and angiogenesis of PDLSCs aggregate was investigated after overexpression and inhibition of miRNA. Periodontal bone defect rat models were established to evaluate the effect of the PDLSCs aggregate and SA-Exo combination on periodontal bone regeneration. Results: SA-Exo could significantly enhance the ECM deposition and angiogenic ability of PDLSCs. The expression of ECM-associated proteins (COL-I, integrinβ1, and fibronectin), angiogenesis-related proteins (PDGF, ANG, TGFβRII), and related pathway (p-SMAD1/5 and p-SMAD2/3) were upregulated in PDLSCs aggregate with SA-Exo. Mechanistically, miR-222 was found relatively abundant in SA-Exo, which promoted ECM deposition and angiogenesis of PDLSCs. In vivo experiment further validated that combinational use of PDLSCs aggregate and SA-Exo promote more bone formation and neovascularization in rat’s periodontal bone defect.Conclusions: SA-Exo-shuttled miR-222 contributes to PDLSCs aggregate engineering by promoting aggregate formation and angiogenesis, which might through activate the TGF-β/SMAD signaling pathway.

scholarly journals Effects of Naringin on Proliferation and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells In Vitro and In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lihua Yin ◽  
Wenxiao Cheng ◽  
Zishun Qin ◽  
Hongdou Yu ◽  
Zhanhai Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Trabecular Structure ◽  
Control Group ◽  
Periodontal Ligament Stem Cells ◽  
Expression Levels ◽  
Proliferation And Differentiation

This study is to explore the osteogenesis potential of the human periodontal ligament stem cells (hPDLSCs) induced by naringin in vitro and in vitro. The results confirmed that 1 μM naringin performs the best effect and a collection of bone-related genes (RUNX2,COL1A2, OPN, and OCN) had significantly higher expression levels compared to the control group. Furthermore, a typical trabecular structure was observed in vivo, surrounded by a large amount of osteoblasts. These results demonstrated that naringin, at a concentration of 1 μM, can efficiently promote the proliferation and differentiation of hPDLSCs both in vitro and in vivo.

Effects of In Vitro Osteogenic Induction on In Vivo Tissue Regeneration by Dental Pulp and Periodontal Ligament Stem Cells

2015 ◽  
Vol 41 (9) ◽  
pp. 1462-1468 ◽  
Author(s):  
Yoonsun Cha ◽  
Mijeong Jeon ◽  
Hyo-Seol Lee ◽  
Seunghye Kim ◽  
Seong-Oh Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tissue Regeneration ◽  
Dental Pulp ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells ◽  
Osteogenic Induction

scholarly journals Mechanical Stress Modulates the RANKL/OPG System of Periodontal Ligament Stem Cells via α7 nAChR in Human Deciduous Teeth: An In Vitro Study

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Yujiang Chen ◽  
Kuan Yang ◽  
Zhifei Zhou ◽  
Lulu Wang ◽  
Yang Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mechanical Stress ◽  
Periodontal Ligament ◽  
Wnt Pathway ◽  
Root Resorption ◽  
Deciduous Teeth ◽  
Hydraulic Pressure ◽  
Periodontal Ligament Stem Cells ◽  
Alizarin Red ◽  
Alpha Bungarotoxin

The aim of this study was to investigate the mechanism by which periodontal ligament stem cells (PDLSCs) modulate root resorption of human deciduous teeth under mechanical stress. In this investigation, the PDLSCs were derived from deciduous and permanent teeth at different stages of root resorption. A cyclic hydraulic pressure was applied on the PDLSCs to mimic chewing forces in the oral environment. The cultured cells were characterized using osteogenic and adipogenic differentiation assays, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting analysis. The PDLSCs exhibited the ability to induce osteoclast differentiation under certain mechanical stresses. As the expressions of RUNX2, alkaline phosphatase (ALP), and osteoprotegerin (OPG) were significantly reduced, the receptor activator of the nuclear factor kappa-B ligand (RANKL) was upregulated increasing the RANKL/OPG ratio. Under hydrodynamic pressure at 0-135 kPa, the expressions of alpha 7 nicotinic acetylcholine receptors (α7 nAChR), p-GSK-3β, and active-β-catenin were markedly upregulated in PDLSCs from unresorbed deciduous teeth. Treatment with the α7 nAChR inhibitor alpha-bungarotoxin (α-BTX) and the Wnt pathway inhibitor DKK1 may reverse the mechanical stress inducing upregulation of RANKL and reduction of RUNX2, ALP, and OPG. Alizarin red staining confirmed these results. The mechanical stress applied on the deciduous tooth PDLSCs can induce osteoclastic effects through upregulation of α7 nAChR and activation of the canonical Wnt pathway. It can be suggested that chewing forces may play a major role at the beginning of the physiological root resorption of deciduous teeth.

scholarly journals Extracellular matrix derived from human urine-derived stem cells enhances the expansion, adhesion, spreading, and differentiation of human periodontal ligament stem cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xue Xiong ◽  
Xiao Yang ◽  
Hongwei Dai ◽  
Gang Feng ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Human Urine ◽  
Periodontal Ligament ◽  
Biological Properties ◽  
Periodontal Ligament Stem Cells ◽  
Essential Components ◽  
Seed Cells

Abstract Background Human periodontal ligament stem cells (hPDLSCs) are one of the most promising types of seed cells in periodontal tissue regeneration. Suitable biomaterials are additional essential components that must cooperate with seed cells for in vivo expansion or in vitro implantation. Extracellular matrix (ECM) derived from mesenchymal stem cells (MSCs) was recently reported to be a promising substrate with which to culture MSCs that could be applied in biomaterial scaffolds or bioink. Human urine-derived stem cells (hUSCs) have several advantages; their collection is non-invasive and easy, and hUSCs are low in cost, potentially making them a suitable and efficient source of ECM. The purpose of this study was to characterize the biological properties of ECM derived from hUSCs (UECM) and evaluate the effects of UECM on hPDLSCs. Methods hPDLSCs grown on ECM derived from hPDLSCs (PECM) and fibronectin-coated tissue culture plastic (TCP) served as control groups. Both hUSCs and hPDLSCs were seeded on TCP and stimulated to produce ECM. After 8 days of stimulation, the samples were decellularized, leaving only ECM. Then, hPDLSCs were seeded onto UECM-, PECM-, and fibronectin-coated TCP and untreated TCP. Results UECM consists of dense bundles of fibers which contain abundant fibronectin. Both UECM and PECM promoted hPDLSC proliferation, attachment, spreading, and differentiation. Between UECM and PECM, UECM enhanced proliferation, osteogenesis, and angiogenesis to a greater extent. Though fibronectin appeared to be the abundant component of UECM, its performance was inferior to that of UECM. Conclusions Our study provides an original perspective on different cell-specific ECMs and suggests UECM as a suitable biomaterial in which to culture hPDLSCs as UECM enhances their biological functions.

scholarly journals Guided Bone Regeneration Using Collagen Scaffolds, Growth Factors, and Periodontal Ligament Stem Cells for Treatment of Peri-Implant Bone Defects In Vivo

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Peer W. Kämmerer ◽  
Malte Scholz ◽  
Maria Baudisch ◽  
Jan Liese ◽  
Katharina Wegner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Periodontal Ligament ◽  
Bone Growth ◽  
Collagen Matrix ◽  
Guided Bone Regeneration ◽  
Periodontal Ligament Stem Cells ◽  
Bone Apposition ◽  
Collagen Powder

Introduction. The aim of the study was an evaluation of different approaches for guided bone regeneration (GBR) of peri-implant defects in an in vivo animal model. Materials and Methods. In minipigs (n=15), peri-implant defects around calcium phosphate- (CaP-; n=46) coated implants were created and randomly filled with (1) blank, (2) collagen/hydroxylapatite/β-tricalcium phosphate scaffold (CHT), (3) CHT + growth factor cocktail (GFC), (4) jellyfish collagen matrix, (5) jellyfish collagen matrix + GFC, (6) collagen powder, and (7) collagen powder + periodontal ligament stem cells (PDLSC). Additional collagen membranes were used for coverage of the defects. After 120 days of healing, bone growth was evaluated histologically (bone to implant contact (BIC;%)), vertical bone apposition (VBA; mm), and new bone height (NBH; %). Results. In all groups, new bone formation was seen. Though, when compared to the blank group, no significant differences were detected for all parameters. BIC and NBH in the group with collagen matrix as well as the group with the collagen matrix + GFC were significantly less when compared to the collagen powder group (all: p<0.003). Conclusion. GBR procedures, in combination with CaP-coated implants, will lead to an enhancement of peri-implant bone growth. There was no additional significant enhancement of osseous regeneration when using GFC or PDLSC.

scholarly journals Cytokines Differently Define the Immunomodulation of Mesenchymal Stem Cells from the Periodontal Ligament

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1222 ◽  
Author(s):  
Christian Behm ◽  
Alice Blufstein ◽  
Johannes Gahn ◽  
Michael Nemec ◽  
Andreas Moritz ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Lymphocytes ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells ◽  
T Lymphocyte Proliferation ◽  
Tnf Α ◽  
Proliferation And Apoptosis ◽  
Cytokine Milieu ◽  
Ifn Γ

Human periodontal ligament stem cells (hPDLSCs) play an important role in periodontal tissue homeostasis and regeneration. The function of these cells in vivo depends largely on their immunomodulatory ability, which is reciprocally regulated by immune cells via cytokines, particularly interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Different cytokines activate distinct signaling pathways and might differently affect immunomodulatory activities of hPDLSCs. This study directly compared the effect of IFN-γ, TNF-α, or IL-1β treated primary hPDLSCs on allogenic CD4+ T lymphocyte proliferation and apoptosis in an indirect co-culture model. The effects of IFN-γ, TNF-α, and IL-1β on the expression of specific immunomodulatory factors such as intoleamine-2,3-dioxygenase-1 (IDO-1), prostaglandin E2 (PGE2), and programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) in hPDLSCs were compared. The contribution of different immunomodulatory mediators to the immunomodulatory effects of hPDLSCs in the indirect co-culture experiments was assessed using specific inhibitors. Proliferation of CD4+ T lymphocytes was inhibited by hPDLSCs, and this effect was strongly enhanced by IFN-γ and IL-1β but not by TNF-α. Apoptosis of CD4+ T lymphocytes was decreased by hPDLSCs per se. This effect was counteracted by IFN-γ or IL-1β. Additionally, IFN-γ, TNF-α, and IL-1β differently regulated all investigated immunomediators in hPDLSCs. Pharmacological inhibition of immunomediators showed that their contribution in regulating CD4+ T lymphocytes depends on the cytokine milieu. Our data indicate that inflammatory cytokines activate specific immunomodulatory mechanisms in hPDLSCs and the expression of particular immunomodulatory factors, which underlies a complex reciprocal interaction between hPDLSCs and CD4+ T lymphocytes.

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