scholarly journals Preconditioning with Melatonin Enhances Osteogenic Differentiation of Dental Pulp Mesenchymal Stem Cells by Regulating MAPK Pathways and Promotes the Efficiency of Bone Regeneration in Calvarial Bone Defects

2021 ◽  
Author(s):  
Ya-Hui Chan ◽  
Kuo-Ning Ho ◽  
Yu-Chieh Lee ◽  
Meng-Jung Chou ◽  
Wei-Zhen Lew ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Dental Pulp ◽  
Bone Defects ◽  
Calvarial Bone ◽  
Alp Activity ◽  
Cox 2

Abstract Background:Mesenchymal stem cell (MSC)-based tissue engineering plays a major role in regenerative medicine. However, the efficiency of MSC transplantation and survival of engrafted stem cells remain challenging. Melatonin can regulate MSC biology. However, its function in the osteogenic differentiation of dental pulp-derived MSCs (DPSCs) remains unclear. We investigated the effects and mechanisms of melatonin preconditioning on the osteogenic differentiation and bone regeneration capacities of DPSCs.Methods:The biological effects and signaling mechanisms of melatonin with different concentrations on DPSCs were evaluated using a proliferation assay, the quantitative alkaline phosphatase (ALP) activity, Alizarin red staining, a real-time polymerase chain reaction, and a western blot in vitro cell culture model. The in vivo bone regeneration capacities were assessed among empty control, MBCP, MBCP+DPSCs, and MBCP+DPSCs+melatonin preconditioning in four-created calvarial bone defects by using micro–computed tomographic, histological, histomorphometric, and immunofluorescence analyses after 4 and 8 weeks of healing.Results:In vitro experiments revealed that melatonin (1, 10, and 100 μM) significantly and concentration-dependently promoted proliferation, surface marker expression (CD 146), ALP activity and extracellular calcium deposition, and osteogenic gene expression of DPSCs (p < 0.05). Melatonin activated the phosphorylation of RUNX-2 and OCN and inhibited COX-2/NF-κB phosphorylation. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPK) P38/ERK signaling was significantly increased in DPSCs treated with 100 μM melatonin, and their inhibitors significantly decreased osteogenic differentiation. In vivo experiments demonstrated that bone defects implanted with MBCP bone-grafting materials and melatonin-preconditioned melatonin exhibited significantly greater bone volume fraction, trabecular bone structural modeling, new bone formation, and osteogenesis-related protein expression than the other three groups at 4 and 8 weeks postoperatively (p < 0.05).Conclusions:These results suggest that melatonin promotes the proliferation and osteogenic differentiation of DPSCs by regulating COX-2/NF-κB and p38/ERK MAPK signaling pathways. Preconditioning DPSCs with melatonin before transplantation can efficiently enhance MSC function and regenerative capacities.

scholarly journals Human Adipose-Derived Mesenchymal Stem Cells-Incorporated Silk Fibroin as a Potential Bio-Scaffold in Guiding Bone Regeneration

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 853 ◽  
Author(s):  
Dewi Sartika ◽  
Chih-Hsin Wang ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Shu-Jen Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Silk Fibroin ◽  
Bone Repair ◽  
Matrix Deposition ◽  
Calvarial Defects

Recently, stem cell-based bone tissue engineering (BTE) has been recognized as a preferable and clinically significant strategy for bone repair. In this study, a pure 3D silk fibroin (SF) scaffold was fabricated as a BTE material using a lyophilization method. We aimed to investigate the efficacy of the SF scaffold with and without seeded human adipose-derived mesenchymal stem cells (hASCs) in facilitating bone regeneration. The effectiveness of the SF-hASCs scaffold was evaluated based on physical characterization, biocompatibility, osteogenic differentiation in vitro, and bone regeneration in critical rat calvarial defects in vivo. The SF scaffold demonstrated superior biocompatibility and significantly promoted osteogenic differentiation of hASCs in vitro. At six and twelve weeks postimplantation, micro-CT showed no statistical difference in new bone formation amongst all groups. However, histological staining results revealed that the SF-hASCs scaffold exhibited a better bone extracellular matrix deposition in the defect regions compared to other groups. Immunohistochemical staining confirmed this result; expression of osteoblast-related genes (BMP-2, COL1a1, and OCN) with the SF-hASCs scaffold treatment was remarkably positive, indicating their ability to achieve effective bone remodeling. Thus, these findings demonstrate that SF can serve as a potential carrier for stem cells, to be used as an osteoconductive bioscaffold for BTE applications.

Association of Dental Pulp Stem Cells and Ricinus Bone Compound in a Model of Bone Defect

2020 ◽  
Vol 3 (3) ◽  
pp. 267-278
Author(s):  
Alan Jesus ◽  
Adriano Jesus ◽  
Flávia Lima ◽  
Luiz Freitas ◽  
Cássio Meira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Bone Defect ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Osteogenic Potential ◽  
Autogenous Bone ◽  
Control Group

Autogenous bone grafting is needed in some bone tissue defects; however, it causes secondary surgical wounds and morbidity. Tissue bioengineering may be an alternative approach for bone regeneration. Here we investigated the osteogenic potential of dental pulp stem cells from deciduous teeth (DPSC) in association with a Ricinus bone compound (RBC) in a model of bone defect. The influence of the biomaterial RBC on the proliferation and osteogenic differentiation of DPSC was assessed in vitro by MTT metabolism and alizarin red staining, respectively. The morphologic analysis was performed using the optic and scanning electron (SEM) microscopies. For the in vivo study, 54 Wistar rats submitted to calvarial defects were filled with RBC or RBC+DPSC. A control group had the defects filled only with blood clots. Analyses were performed 15, 30 and 60 days after treatment using digital radiography, optical microscopy, SEM and chemical analysis by electron dispersive spectroscopy. The Ricinus bone compound (RBC) did not inhibit the osteogenic differentiation in vitro. No spontaneous regeneration was observed in the control group. The area of the calvarial defect of the RBC+DPSC group showed greater radiopacity on day 15. The RBC presented no reabsorption, was biocompatible and showed osteointegration, working as a mechanical filling. Only sparse ossification areas were found and those were larger and more developed on the RBC+DPSC group when compared to animals treated only with RBC. RBC in association with DPSC is a promising combination for applications in bone regeneration.  

scholarly journals Comparing the Osteogenic Potentials and Bone Regeneration Capacities of Bone Marrow and Dental Pulp Mesenchymal Stem Cells in a Rabbit Calvarial Bone Defect Model

2019 ◽  
Vol 20 (20) ◽  
pp. 5015 ◽  
Author(s):  
Yu-Chieh Lee ◽  
Ya-Hui Chan ◽  
Sung-Chih Hsieh ◽  
Wei-Zhen Lew ◽  
Sheng-Wei Feng
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Dental Pulp ◽  
New Bone Formation ◽  
Trilineage Differentiation ◽  
Empty Control

The bone regeneration efficiency of bone marrow mesenchymal stem cells (BMSCs) and dental pulp mesenchymal stem cells (DPSCs) combined with xenografts in the craniofacial region remains unclear. Accordingly, this study commenced by comparing the cell morphology, cell proliferation, trilineage differentiation, mineral synthesis, and osteogenic gene expression of BMSCs and DPSCs in vitro. Four experimental groups (empty control, Bio-Oss only, Bio-Oss+BMSCs, and Bio-Oss+DPSCs) were then designed and implanted in rabbit calvarial defects. The BMSCs and DPSCs showed a similar morphology, proliferative ability, surface marker profile, and trilineage-differentiation potential in vitro. However, the BMSCs exhibited a higher mineral deposition and expression levels of osteogenic marker genes, including alkaline phosphatase (ALP), runt related transcription factor 2 (RUNX2), and osteocalcin (OCN). In the in vivo studies, the bone volume density in both MSC groups was significantly greater than that in the empty control or Bio-Oss only group. Moreover, the new bone formation and Collagen I / osteoprotegerin protein expressions of the scaffold+MSC groups were higher than those of the Bio-Oss only group. Finally, the Bio-Oss+BMSC and Bio-Oss+DPSC groups had a similar bone mineral density, new bone formation, and osteogenesis-related protein expression. Overall, the DPSCs seeded on Bio-Oss matched the bone regeneration efficacy of BMSCs in vivo and hence appear to be a promising strategy for craniofacial defect repair in future clinical applications.

Strontium folate loaded biohybrid scaffolds seeded with dental pulp stem cells induce in vivo bone regeneration in critical sized defects

2016 ◽  
Vol 4 (11) ◽  
pp. 1596-1604 ◽  
Author(s):  
Marcela Martin-del-Campo ◽  
Raul Rosales-Ibañez ◽  
Keila Alvarado ◽  
Jose G. Sampedro ◽  
Christian A. Garcia-Sepulveda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Dental Pulp ◽  
Bone Defects ◽  
Dental Pulp Stem Cells ◽  
Critical Bone Defects ◽  
Complete Regeneration

Strontium folate loaded biohybrid scaffolds enhance dental pulp stem cells replication and differentiation, promoting complete regeneration of critical bone defects.

scholarly journals Human Serum Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50542 ◽  
Author(s):  
Alessandra Pisciotta ◽  
Massimo Riccio ◽  
Gianluca Carnevale ◽  
Francesca Beretti ◽  
Lara Gibellini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Serum ◽  
Osteogenic Differentiation ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Human Dental Pulp

scholarly journals Cathelicidin LL37 Promotes Osteogenic Differentiation in vitro and Bone Regeneration in vivo

2021 ◽  
Vol 9 ◽  
Author(s):  
Lunhao Li ◽  
Yiyu Peng ◽  
Qingyue Yuan ◽  
Jing Sun ◽  
Ai Zhuang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Antibacterial Properties ◽  
Bone Defects ◽  
Optimum Concentration ◽  
Calvarial Defect ◽  
Defect Model ◽  
Calvarial Bone ◽  
Rat Calvarial Defect

Different types of biomaterials have been used to repair the defect of bony orbit. However, exposure and infections are still critical risks in clinical application. Biomaterials with characteristics of osteogenesis and antibiosis are needed for bone regeneration. In this study, we aimed to characterize the antimicrobial effects of cathelicidin-LL37 and to assess any impacts on osteogenic activity. Furthermore, we attempted to demonstrate the feasibility of LL37 as a potential strategy in the reconstruction of clinical bone defects. Human adipose-derived mesenchyme stem cells (hADSCs) were cultured with different concentrations of LL37 and the optimum concentration for osteogenesis was selected for further in vitro studies. We then evaluated the antibiotic properties of LL37 at the optimum osteogenic concentration. Finally, we estimated the efficiency of a PSeD/hADSCs/LL37 combined scaffold on reconstructing bone defects in the rat calvarial defect model. The osteogenic ability on hADSCs in vitro was shown to be dependent on the concentration of LL37 and reached a peak at 4 μg/ml. The optimum concentration of LL37 showed good antimicrobial properties against Escherichia coli and Staphylococcus anurans. The combination scaffold of PSeD/hADSCs/LL37 showed superior osteogenic properties compared to the PSeD/hADSCs, PSeD, and control groups scaffolds, indicating a strong bone reconstruction effect in the rat calvarial bone defect model. In Conclusion, LL37 was shown to promote osteogenic differentiation in vitro as well as antibacterial properties. The combination of PSeD/hADSCs/LL37 was advantageous in the rat calvarial defect reconstruction model, showing high potential in clinical bone regeneration.

In vitro and in vivo osteogenesis up-regulated by two-dimensional nanosheets through a macrophage-mediated pathway

2021 ◽  
Author(s):  
Haoming Liu ◽  
Gaojie Yang ◽  
Hao Yin ◽  
Zhenxing Wang ◽  
Chunyuan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Calcium Phosphate ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Two Dimensional ◽  
M2 Polarization

Two-dimensional calcium phosphate nanomaterials are able to stimulate in vitro osteogenic differentiation of stem cells and in vivo bone regeneration by inducing M2 polarization of macrophages, rather than manipulating stem cells’ fate directly.

scholarly journals Osteogenic Differentiation Potential of Human Bone Marrow and Amniotic Fluid-Derived Mesenchymal Stem Cells in Vitro & in Vivo

2019 ◽  
Vol 7 (4) ◽  
pp. 507-515 ◽  
Author(s):  
Eman E. A. Mohammed ◽  
Mohamed El-Zawahry ◽  
Abdel Razik H. Farrag ◽  
Nahla N. Abdel Aziz ◽  
Wessam Sharaf-ElDin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Amniotic Fluid ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Differentiation Potential

BACKGROUND: Cell therapies offer a promising potential in promoting bone regeneration. Stem cell therapy presents attractive care modality in treating degenerative conditions or tissue injuries. The rationale behind this is both the expansion potential of stem cells into a large cell population size and its differentiation abilities into a wide variety of tissue types, when given the proper stimuli. A progenitor stem cell is a promising source of cell therapy in regenerative medicine and bone tissue engineering. AIM: This study aimed to compare the osteogenic differentiation and regenerative potentials of human mesenchymal stem cells derived from human bone marrow (hBM-MSCs) or amniotic fluid (hAF-MSCs), both in vitro and in vivo studies. SUBJECTS AND METHODS: Human MSCs, used in this study, were successfully isolated from two human sources; the bone marrow (BM) and amniotic fluid (AF) collected at the gestational ages of second or third trimesters. RESULTS: The stem cells derived from amniotic fluid seemed to be the most promising type of progenitor cells for clinical applications. In a pre-clinical experiment, attempting to explore the therapeutic application of MSCs in bone regeneration, Rat lumbar spines defects were surgically created and treated with undifferentiated and osteogenically differentiated MSCs, derived from BM and second trimester AF. Cells were loaded on gel-foam scaffolds, inserted and fixed in the area of the surgical defect. X-Ray radiography follows up, and histopathological analysis was done three-four months post- operation. The transplantation of AF-MSCs or BM-MSCs into induced bony defects showed promising results. The AF-MSCs are offering a better healing effect increasing the likelihood of achieving successful spinal fusion. Some bone changes were observed in rats transplanted with osteoblasts differentiated cells but not in rats transplanted with undifferentiated MSCs. Longer observational periods are required to evaluate a true bone formation. The findings of this study suggested that the different sources; hBM-MSCs or hAF-MSCs exhibited remarkably different signature regarding the cell morphology, proliferation capacity and osteogenic differentiation potential CONCLUSIONS: AF-MSCs have a better performance in vivo bone healing than that of BM-MSCs. Hence, AF derived MSCs is highly recommended as an alternative source to BM-MSCs in bone regeneration and spine fusion surgeries. Moreover, the usage of gel-foam as a scaffold proved as an efficient cell carrier that showed bio-compatibility with cells, bio-degradability and osteoinductivity in vivo.

scholarly journals Bone Regeneration: A Novel Osteoinductive Function of Spongostan by the Interplay between Its Nano- and Microtopography

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 654
Author(s):  
Thomas Vordemvenne ◽  
Dirk Wähnert ◽  
Julian Koettnitz ◽  
Madlen Merten ◽  
Nadine Fokin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Tumor Resection ◽  
Sio2 Nanoparticles ◽  
Collagen Sponge ◽  
Human Stem Cells ◽  
Scaffold Materials

Scaffold materials for bone regeneration are crucial for supporting endogenous healing after accidents, infections, or tumor resection. Although beneficial impacts of microtopological or nanotopological cues in scaffold topography are commonly acknowledged, less consideration is given to the interplay between the microscale and nanoscale. Here, micropores with a 60.66 ± 24.48 µm diameter ordered by closely packed collagen fibers are identified in pre-wetted Spongostan, a clinically-approved collagen sponge. On a nanoscale level, a corrugated surface of the collagen sponge is observable, leading to the presence of 32.97 ± 1.41 nm pores. This distinct micro- and nanotopography is shown to be solely sufficient for guiding osteogenic differentiation of human stem cells in vitro. Transplantation of Spongostan into a critical-size calvarial rat bone defect further leads to fast regeneration of the lesion. However, masking the micro- and nanotopographical cues using SiO2 nanoparticles prevents bone regeneration in vivo. Therefore, we demonstrate that the identified micropores allow migration of stem cells, which are further driven towards osteogenic differentiation by scaffold nanotopography. The present findings emphasize the necessity of considering both micro- and nanotopographical cues to guide intramembranous ossification, and might provide an optimal cell- and growth-factor-free scaffold for bone regeneration in clinical settings.

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