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  • 1
    Online Resource
    Online Resource
    Exploring a Chemotactic Role for EVs from Progenitor Cell Populations of Human Exfoliated Deciduous Teeth for Promoting Migration of Naïve BMSCs in Bone Repair Process
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-3-17), p. 1-7
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-3-17), p. 1-7
    Abstract: Mobilization of naïve bone marrow mesenchymal stromal cells (BMSCs) is crucial to desired bone regeneration in both orthopedic and dental contexts. In such conditions, mesenchymal progenitor cell populations from human exfoliated deciduous teeth (SHEDs) present advantageous multipotent properties with easy accessibility which makes them a good candidate in both bone and periodontal tissue regeneration. Extracellular vesicles (EVs) are a functional membranous structure which could participate in multiple cell interactions and imitate the biological functions of their parenting cells largely. To assess their ability to mobilize naïve BMSCs in the bone repair process, Nanosight Tracking Analysis (NTA) and Enzyme-Linked Immunosorbent Assays (ELISA) were performed to illustrate the composition and functional contents of EV samples derived from SHEDs with different culturing time (24 h, 48 h, and 72 h). Afterwards, the Boyden chamber assay was performed to compare their capacity for mobilizing naïve BMSCs. One-way analysis of variance (ANOVA) with a post hoc Turkey test was performed for statistical analysis. SHEDs-derived EVs collected from 24 h, 48 h, and 72 h time points, namely, EV24, EV48, and EV72, were mainly secreted as exosomes and tended to reform into smaller size as a result of sonication indicated by NTA results. Moreover, different EV groups were found to be abundant with multiple growth factors including transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor-2 (FGF-2) given the detections through ELISA. Boyden chamber assays implied the migratory efficiency of BMSCs driven by EVs at varying concentrations. However, the results showed that migration of BMSCs driven by different EV groups was not statistically significant even with chemotactic factors contained ( P 〉 0.05 ). Taken together, these data suggest that EVs derived from SHEDs are secreted in functional forms and present a potential of mobilizing naïve BMSCs, which may propose their relevance in assisting bone regeneration.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/6681771
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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  • 2
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    The Four Pillars for Successful Regenerative Therapy in Endodontics: Stem Cells, Biomaterials, Growth Factors, and Their Synergistic Interactions
    Hindawi Limited ; 2022
    In:  Stem Cells International Vol. 2022 ( 2022-9-19), p. 1-17
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2022 ( 2022-9-19), p. 1-17
    Abstract: Endodontics has made significant progress in regenerative approaches in recent years, thanks to advances in biologically based procedures or regenerative endodontic therapy (RET). In recent years, our profession has witnessed a clear conceptual shift in this therapy. RET was initially based on a blood clot induced by apical bleeding without harvesting the patient’s cells or cell-free RET. Later, the RET encompassed the three principles of tissue engineering, stromal/stem cells, scaffolds, and growth factors, aiming for the regeneration of a functional dentin pulp complex. The regenerated dental pulp will recover the protective mechanisms including innate immunity, tertiary dentin formation, and pain sensitivity. This comprehensive review covers the basic knowledge and practical information for translational applications of stem cell-based RET and tissue engineering procedures for the regeneration of dental pulp. It will also provide overall information on the emerging technologies in biological and synthetic matrices, biomaterials, and signaling molecules, recent advances in stem cell therapy, and updated experimental results. This review brings useful and timely clinical evidence for practitioners to understand the challenges faced for a successful cell-based RET and the importance of preserving or reestablishing tooth vitality. The clinical translation of these current bioengineering approaches will undoubtedly be beneficial to the future practice of endodontics.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2022/1580842
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
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  • 3
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    Graphene Oxide Quantum Dots Promote Osteogenic Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth via the Wnt/β-Catenin Signaling Pathway
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-2-5), p. 1-12
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-2-5), p. 1-12
    Abstract: Graphene oxide quantum dots (GOQDs) are a carbon nanomaterial with broad potential for application in the field of nanomaterial biomedicine. Stem cells from human exfoliated deciduous teeth (SHEDs) play an important role in tissue engineering and regenerative medicine. This study investigated the effects of GOQDs on SHED osteogenic differentiation. GOQDs were synthesized; then, the proliferation of SHEDs incubated in GOQDs at different concentrations was evaluated; and the live cells were observed. We observed that live SHEDs incubated in GOQDs emitted green fluorescence in the absence of chemical dyes, and 1, 10, and 50 μg/mL GOQDs significantly promoted SHED proliferation. Culture with the osteogenic induction medium containing 10 μg/mL GOQDs induced calcium nodule formation, increased alkaline phosphatase (ALP) activity, and upregulated SHED mRNA and protein levels of OCN, RUNX2, COL I, and β-catenin. With the addition of Dickkopf 1 (DKK-1) or β-catenin knockdown, expression levels of the above mRNAs and proteins were decreased in GOQD-treated SHEDs. In summary, at a concentration of 10 μg/mL, GOQDs promote SHED proliferation and osteogenic differentiation via the Wnt/β-catenin signaling pathway. This work provides new ideas and fundamental information on interactions between GOQDs and SHEDs that are relevant for the biomedical engineering field.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/8876745
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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  • 4
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    Adipose-Derived Stem Cell-Derived Extracellular Vesicles Inhibit the Fibrosis of Fibrotic Buccal Mucosal Fibroblasts via the MicroRNA-375/FOXF1 Axis
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-6-22), p. 1-15
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-6-22), p. 1-15
    Abstract: Oral submucous fibrosis (OSF) is a precancerous lesion. Adipose-derived stem cell- (ADSC-) derived extracellular vesicles (EVs) (ADSC-EVs) regulate multiple oral diseases. Hence, this study explored the mechanism of ADSC-EVs in OSF. ADSCs were transduced with microRNA- (miR-) 375 mimic. ADSC-EVs and miR-375-overexpressed ADSC-EVs (EVs-miR-375) were extracted and identified. miR-375 expression in EVs and fibrotic buccal mucosal fibroblasts (fBMFs) was detected. EV uptake by fBMFs was observed. The targeted relationship between miR-375 and forkhead box protein F1 (FOXF1) was predicted and verified. After EVs-miR-375 treatment or FOXF1 overexpression, fBMF cell proliferation, migration, invasion, and apoptosis were evaluated, and levels of apoptosis-related proteins (cleaved-caspase-3, Bax, and Bcl-2) and fibrosis markers (α-SMA, collagen I, and collagen III) were detected. Functional rescue experiments were further performed to verify the role of the miR-375/FOXF1 axis in OSF. miR-375 was notably upregulated in EVs-miR-375 and EVs-miR-375-treated fBMFs (all P 〈 0.001 ). ADSC-EVs carried miR-375 into fBMFs. fBMFs can internalize ADSC-EVs. EVs-miR-375 treatment markedly inhibited fBMF cell proliferation, migration, invasion, and fibrosis and promoted apoptosis (all P 〈 0.01 ). Moreover, miR-375 targeted FOXF1 in fBMFs. FOXF1 overexpression promoted fBMF cell biological behaviors and fibrosis, which were reversed after EVs-miR-375 treatment ( P 〈 0.01 or P 〈 0.001 ). We highlighted that ADSC-EVs inhibited fBMF fibrosis and then suppressed OSF progression via the miR-375/FOXF1 axis.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/9964159
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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  • 5
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    DPSCs Protect Architectural Integrity and Alleviate Intervertebral Disc Degeneration by Regulating Nucleus Pulposus Immune Status
    Hindawi Limited ; 2022
    In:  Stem Cells International Vol. 2022 ( 2022-10-15), p. 1-17
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2022 ( 2022-10-15), p. 1-17
    Abstract: Intervertebral disc (IVD) degeneration is the primary cause for low back pain that has a high prevalence in modern society and poses enormous economic burden on patients. Few effective therapeutic strategies are available for IVD degeneration treatment. To understand the biological effects of dental pulp stem cells (DPSCs) on nucleus pulposus (NP) cells, we carried out RNA sequencing, bioinformatic analysis which unveiled gene expression differences, and pathway variation in primarily isolated patients’ NP cells after treatment with DPSCs supernatant. Western blot and immunofluorescence were used to verify these molecular alterations. Besides, to evaluate the therapeutic effect of DPSCs in IVD degeneration treatment, DPSCs were injected into a degeneration rat model in situ, with treatment outcome measured by micro-CT and histological analysis. RNA sequencing and in vitro experiments demonstrated that DPSCs supernatant could downregulate NP cells’ inflammation-related NF-κB and JAK-STAT pathways, reduce IL-6 production, increase collagen II expression, and mitigate apoptosis. In vivo results showed that DPSCs treatment protected the integrity of the disc structure, alleviated extracellular matrix degradation, and increased collagen fiber expression. In this study, we verified the therapeutic effect of DPSCs in an IVD degeneration rat model and elucidated the underlying molecular mechanism of DPSCs treatment, which provides a foundation for the application of DPSCs in IVD degeneration treatment.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2022/7590337
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
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  • 6
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    Characterization and Study of Gene Expression Profiles of Human Periodontal Mesenchymal Stem Cells in Spheroid Cultures by Transcriptome Analysis
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-10-19), p. 1-18
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-10-19), p. 1-18
    Abstract: A spheroid is known as a three-dimensional culture model, which better simulates the physiological conditions of stem cells. This study is aimed at identifying genes specifically expressed in spheroid-cultured human periodontal ligament mesenchymal stem cells (hPDLMSCs) using RNA-seq analysis to evaluate their functions. Transcriptome analysis was performed using spheroid and monolayer cultures of hPDLMSCs from four patients. Cluster and Gene Ontology analyses revealed that genes involved in cell-cell adhesion as well as the G2/M and G1/S transitions of mitotic cell cycles were strongly expressed in the monolayer culture group. However, genes involved in the negative regulation of cell proliferation, histone deacetylation, and bone morphogenetic protein signaling were strongly expressed in the spheroid culture group. We focused on the transcription factor nuclear receptor subfamily 4 group A member 2 (NR4A2) among the genes that were strongly expressed in the spheroid culture group and analyzed its function. To confirm the results of the transcriptome analysis, we performed real-time polymerase chain reaction and western blotting analyses. Interestingly, we found that the mRNA and protein expressions of NR4A2 were strongly expressed in the spheroid-cultured hPDLMSCs. Under osteogenic differentiation conditions, we used siRNA to knock down NR4A2 in spheroid-cultured hPDLMSCs to verify its role in osteogenesis. We found that NR4A2 knockdown significantly increased the levels of mRNA expression for osteogenesis-related genes alkaline phosphatase (ALP), Osteopontin (OPN), and type 1 collagen (COL1) (Student’s paired t -test, p 〈 0.05 ). ALP activity was also significantly increased when compared to the negative control group (Student’s paired t -test, p 〈 0.05 ). Additionally, spheroid-cultured hPDLMSCs transfected with siNR4A2 were cultured for 12 days, resulting in the formation of significantly larger calcified nodules compared to the negative control group (Student’s paired t -test, p 〈 0.05 ). On the other hand, NR4A2 knockdown in hPDLMSC spheroid did not affect the levels of chondrogenesis and adipogenesis-related genes under chondrogenic and adipogenic conditions. These results suggest that NR4A2 negatively regulates osteogenesis in the spheroid culture of hPDLMSCs.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/5592804
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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  • 7
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    Early Osteogenic Differentiation Stimulation of Dental Pulp Stem Cells by Calcitriol and Curcumin
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-5-23), p. 1-7
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-5-23), p. 1-7
    Abstract: Curcumin, as a natural phenolic substance, is extracted from the rhizome of Curcuma longa (turmeric), which is effective in bone healthfulness. Calcitriol is an effective hormone in regulating bone remodeling and mineral homeostasis and immune response. Mesenchymal stem cells (MSCs) are found in most dental tissues and resemble bone marrow-derived MSCs. In this work, we investigated the effect of combination and individual treatment of curcumin and calcitriol on early osteogenic differentiation of dental pulp stem cells (DPSCs). Early osteogenic differentiation was evaluated and confirmed by the gene expression level of ALP and its activity. Curcumin individually and in combination with calcitriol increased ALP activity and osteoblast-specific mRNA expression of ALP when DPSCs were cultured in an osteogenic medium. Calcitriol alone increased the enzyme more than in combination with curcumin. These findings demonstrate that curcumin can induce early osteogenic differentiation of DPSCs like calcitriol as a potent stimulant of osteogenesis.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/9980137
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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  • 8
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    Enamel Matrix Derivative Enhances the Odontoblastic Differentiation of Dental Pulp Stem Cells via Activating MAPK Signaling Pathways
    Hindawi Limited ; 2022
    In:  Stem Cells International Vol. 2022 ( 2022-4-28), p. 1-16
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2022 ( 2022-4-28), p. 1-16
    Abstract: The odontoblastic differentiation of dental pulp stem cells (DPSCs) contributes to pulp-dentin regeneration. Enamel matrix derivative (EMD) is considered to be a critical epithelial signal to induce cell differentiation during odontogenesis and has been widely applied to clinical periodontal tissue regeneration. The purpose of this study was to explore the effect of EMD on DPSCs proliferation and odontoblastic differentiation, as well as the underlying mechanisms. We conducted in vitro and in vivo researches to get a comprehensive understanding of EMD. In vitro phase: cell proliferation was assessed by a cell counting kit-8 (CCK-8) assay; then, alkaline phosphatase (ALP) activity and staining, alizarin red staining, real-time RT-PCR, and western blot analysis were conducted to determine the odontoblastic potential and involvement of MAPK signaling pathways. In vivo phase: after ensuring the biocompatibility of VitroGel 3D-RGD via scanning electron microscopy (SEM), the hydrogel mixture was subcutaneously injected into nude mice followed by histological and immunohistochemical analyses. The results revealed that EMD did not interfere with DPSCs proliferation but promoted the odontoblastic differentiation of DPSCs in vitro and in vivo. Furthermore, blocking the MAPK pathways suppressed the EMD-enhanced differentiation of DPSCs. Finally, VitroGel 3D-RGD could well support the proliferation, differentiation, and regeneration of DPSCs. Overall, this study demonstrates that EMD enhances the odontoblastic differentiation of DPSCs through triggering MAPK signaling pathways. The findings provide a new insight into the mechanism by which EMD affects DPSCs differentiation and proposes EMD as a promising candidate for future stem cell therapy in endodontics.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2022/2236250
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
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  • 9
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    Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-1-9), p. 1-12
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-1-9), p. 1-12
    Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/8850820
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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  • 10
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    A Two-Stage Process for Differentiation of Wharton’s Jelly-Derived Mesenchymal Stem Cells into Neuronal-like Cells
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-5-28), p. 1-17
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-5-28), p. 1-17
    Abstract: With no permanent cure for neurodegenerative diseases, the symptoms reappear shortly after the withdrawal of medicines. A better treatment outcome can be expected if the damaged neurons are partly replaced by functional neurons and/or they are repaired using trophic factors. In this regard, safe cell therapy has been considered as a potential alternative to conventional treatment. Here, we have described a two-stage culture process to differentiate Wharton Jelly mesenchymal stem cells (WJ-MSCs) into neuronal-like cells in the presence of various cues involved in neurogenesis. The fate of cells at the end of each stage was analyzed at the morphometric, transcriptional, and translational levels. In the first stage of priming, constitutively, wingless-activated WJ-MSCs crossed the lineage boundary in favor of neuroectodermal lineage, identified by the loss of mesenchymal genes with concomitant expression of neuron-specific markers, like SOX1, PAX6, NTRK1, and NEUROD2. Neuronal-like cells formed in the second stage expressed many mature neuronal proteins like Map2, neurofilament, and Tuj1 and possessed axon hillock-like structures. In conclusion, the differentiation of a large number of neuronal-like cells from nontumorigenic and trophic factors secreting WJ-MSCs promises the development of a therapeutic strategy to treat neurodegenerative diseases.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/6631651
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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