Three-dimensional Spheroid Culture Enhances Multipotent Differentiation and Stemness Capacities of Human Dental Pulp‐derived Mesenchymal Stem Cells by Modulating MAPK and NF-kB Signaling Pathways

Chan, Ya Hui; Lee, Yu Chieh; Hung, Chia Yi; Yang, Pi Ju; Lai, Pin Chuang; Feng, Sheng

doi:10.1007/s12015-021-10172-4

Cited by 40 publications

(45 citation statements)

References 49 publications

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“…However, the BMSCs showed higher osteogenic and chondrogenic differentiation potential, whereas the DPSCs showed higher CFU and proliferation capacities ( Figure 2 ). These results are consistent with those of previous in vitro studies [ 27 , 44 , 45 , 46 ]. Compared with BMSCs, DPSCs provide the advantages of harvesting cells from discarded teeth in a noninvasive manner, a high proliferation rate, a high odontogenic/osteogenic differentiation potential, and excellent immunomodulatory properties [ 31 , 47 , 48 ].…”

Section: Discussionsupporting

confidence: 94%

“…Simultaneously, the DPSCs exhibited a stronger antiapoptotic ability under the microenvironment of oxidative stress [ 45 ]. However, in vivo studies have reported controversial results for new bone formation by using DPSCs and BMSCs, and their efficiency in comparison with the autogenous bone was not examined in previous studies [ 27 , 44 , 47 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, extrinsic factors such as the health status of the donor, aging, and a low oxygen level can significantly and negatively affect the efficiency of clinical cell transplantation [ 49 , 55 ]. Although overcoming extensive bone loss and improving the therapeutic efficacy remain challenging, novel MSC-based bone regeneration strategies, including cytotherapy, 3D culture, preconditioning, and cell-free approaches, appear promising for curing severe large bone defects, irrespective of the regular or diseased microenvironments [ 15 , 27 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…The DPSCs were isolated from freshly extracted incisors by using the direct outgrowth method described previously [ 22 , 27 ]. The pulp tissue was carefully removed from each tooth by using a sterile mortar and pestle.…”

Section: Methodsmentioning

confidence: 99%

“…DPSCs, which are dental pulp-derived MSCs, have been proposed as a potential cell source for bone tissue engineering because of their high feasibility, easy access, and noninvasive harvesting without ethical concerns [ 21 , 22 ]. DPSCs have exhibited strong angiogenic and osteogenic potential in vitro and in vivo with the ability to directly differentiate into or interact with endothelial cells and osteoblasts [ 18 , 23 , 24 , 25 , 26 , 27 ]. In addition, the DPSCs demonstrated a strong potential for proliferation and differentiation, along with paracrine properties; the in vivo implantation of DPSCs promoted bone regeneration and repaired bone defects [ 22 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Different Bone Grafting Materials and Mesenchymal Stem Cells on Bone Regeneration: A Micro-Computed Tomography and Histomorphometric Study in a Rabbit Calvarial Defect Model

Shiu

Lee

Chen

et al. 2021

IJMS

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This study evaluated the new bone formation potential of micro–macro biphasic calcium phosphate (MBCP) and Bio-Oss grafting materials with and without dental pulp-derived mesenchymal stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in a rabbit calvarial bone defect model. The surface structure of the grafting materials was evaluated using a scanning electron microscope (SEM). The multipotent differentiation characteristics of the DPSCs and BMSCs were assessed. Four circular bone defects were created in the calvarium of 24 rabbits and randomly allocated to eight experimental groups: empty control, MBCP, MBCP+DPSCs, MBCP+BMSCs, Bio-Oss+DPSCs, Bio-Oss+BMSCs, and autogenous bone. A three-dimensional analysis of the new bone formation was performed using micro-computed tomography (micro-CT) and a histological study after 2, 4, and 8 weeks of healing. Homogenously porous structures were observed in both grafting materials. The BMSCs revealed higher osteogenic differentiation capacities, whereas the DPSCs exhibited higher colony-forming units. The micro-CT and histological analysis findings for the new bone formation were consistent. In general, the empty control showed the lowest bone regeneration capacity throughout the experimental period. By contrast, the percentage of new bone formation was the highest in the autogenous bone group after 2 (39.4% ± 4.7%) and 4 weeks (49.7% ± 1.5%) of healing (p < 0.05). MBCP and Bio-Oss could provide osteoconductive support and prevent the collapse of the defect space for new bone formation. In addition, more osteoblastic cells lining the surface of the newly formed bone and bone grafting materials were observed after incorporating the DPSCs and BMSCs. After 8 weeks of healing, the autogenous bone group (54.9% ± 6.1%) showed a higher percentage of new bone formation than the empty control (35.3% ± 0.5%), MBCP (38.3% ± 6.0%), MBCP+DPSC (39.8% ± 5.7%), Bio-Oss (41.3% ± 3.5%), and Bio-Oss+DPSC (42.1% ± 2.7%) groups. Nevertheless, the percentage of new bone formation did not significantly differ between the MBCP+BMSC (47.2% ± 8.3%) and Bio-Oss+BMSC (51.2% ± 9.9%) groups and the autogenous bone group. Our study results demonstrated that autogenous bone is the gold standard. Both the DPSCs and BMSCs enhanced the osteoconductive capacities of MBCP and Bio-Oss. In addition, the efficiency of the BMSCs combined with MBCP and Bio-Oss was comparable to that of the autogenous bone after 8 weeks of healing. These findings provide effective strategies for the improvement of biomaterials and MSC-based bone tissue regeneration.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Different Bone Grafting Materials and Mesenchymal Stem Cells on Bone Regeneration: A Micro-Computed Tomography and Histomorphometric Study in a Rabbit Calvarial Defect Model

Shiu

Lee

Chen

et al. 2021

IJMS

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Wnt3a‐Loaded Hydroxyapatite Nanowire@Mesoporous Silica Core−Shell Nanocomposite Promotes the Regeneration of Dentin−Pulp Complex via Angiogenesis, Oxidative Stress Resistance, and Odontogenic Induction of Stem Cells

Luo

Deng

Jin

et al. 2023

Adv Healthcare Materials

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Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a‐loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a‐HANW@MpSi) core−shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a‐HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a‐HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin–pulp complex‐like tissues and blood vessels by Wnt3a‐HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a‐HANW@MpSi in treatments of dental pulp exposure.

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Introduction to Natural Product-Based Tissue Engineering

Sinha,

Nath,

Borkataky

2024

Natural Product Inspired Scaffolds

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Three-dimensional Spheroid Culture Enhances Multipotent Differentiation and Stemness Capacities of Human Dental Pulp‐derived Mesenchymal Stem Cells by Modulating MAPK and NF-kB Signaling Pathways

Cited by 40 publications

References 49 publications

Effect of Different Bone Grafting Materials and Mesenchymal Stem Cells on Bone Regeneration: A Micro-Computed Tomography and Histomorphometric Study in a Rabbit Calvarial Defect Model

Effect of Different Bone Grafting Materials and Mesenchymal Stem Cells on Bone Regeneration: A Micro-Computed Tomography and Histomorphometric Study in a Rabbit Calvarial Defect Model

Wnt3a‐Loaded Hydroxyapatite Nanowire@Mesoporous Silica Core−Shell Nanocomposite Promotes the Regeneration of Dentin−Pulp Complex via Angiogenesis, Oxidative Stress Resistance, and Odontogenic Induction of Stem Cells

Introduction to Natural Product-Based Tissue Engineering

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