Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts

Yan, Ming; Fu, Lingling; Nada, Ola A.; Chen, Liming; Gosau, Martin; Smeets, Ralf; Han, Feng; Friedrich, Reinhard E

doi:10.3390/cells10071803

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…In principle, this means that autogenous sources of cell and tissue regeneration are available for NF1 patients (11). This and previous studies show that the constitutive loss of the NF1 gene does not affect the ability of DPSCs to differentiate according to the chosen conditioning of the environment (43)(44)(45). Until now, it was unknown whether DPSCs from teeth in this tumor area have the same differentiation capacity as DPSCs from NF1 patients who have not developed this facial tumor.…”

Section: Discussionmentioning

confidence: 85%

Characterization of Dental Pulp Stem Cell Populations in the Teeth of Patients With Neurofibromatosis Type 1 - Therapeutic Potential for Bone Tissue Engineering

Yan

Wang

Speth

et al. 2023

In Vivo

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Background/Aim: Neurofibromas (NF) are the most common benign nerve sheath tumors in the tongue, gingiva, major salivary glands, and jaw bones. Nowadays, tissue engineering is a revolutionary technique for reconstructing tissues. To explore the feasibility of using stem cells derived from NF teeth to treat orofacial bone defects, the differences in cell biological properties between an NF teeth group and Normal teeth group. Patients and Methods: The intra-dental pulp tissues from each tooth were extracted. The cell survival rates, morphology, proliferation rates, cell activity, and differentiation abilities were contrastively analyzed between the NF teeth group and Normal teeth group. Results: Between the two groups, there were no differences in the primary generation (P0) cells (p>0.05), the cell yield, and the time required for the cells to grow out of the pulp tissue and attach to the culture plate. Furthermore, no differences were found at the first generation (passage) between the two groups in colony formation rate and cell survival rate. The proliferation capacity, cell growth curve, and surface marker expression of dental pulp cells was not altered in the third generation (p>0.05). Conclusion: Dental pulp stem cells from NF teeth were successfully obtained and were not different from normal dental pulp stem cells. Although, clinical research using tissue-engineered bone to repair bone defects is still in its infancy, it will eventually enter the clinic and become a routine means of bone defect reconstruction treatment as related disciplines and technologies develop.

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Section: Discussionmentioning

confidence: 85%

Characterization of Dental Pulp Stem Cell Populations in the Teeth of Patients With Neurofibromatosis Type 1 - Therapeutic Potential for Bone Tissue Engineering

Yan

Wang

Speth

et al. 2023

In Vivo

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“…Meanwhile, hDPSCs have been shown to have potent immunomodulatory functions in treating systemic lupus erythematosus (SLE) in the SLE MRL/lpr mouse model ( 6 ). Yan et al also indicated that hDPSCs could inhibit the progression of fibrosis in hypertrophic keloids ( 7 ). In addition, they are available from various tissue sources, including dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, periodontal ligament stem cells and dental follicle progenitor cells ( 8 ), and are highly available during tooth extraction, making them a reliable source for periodontal tissue regeneration techniques ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Dental pulp stem cells induce anti-inflammatory phenotypic transformation of macrophages to enhance osteogenic potential via IL-6/GP130/STAT3 signaling

Liu¹,

Li²,

Chen³

et al. 2023

Ann Transl Med

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Background Periodontitis is a major oral condition and current treatment outcomes can be unsatisfactory. Macrophages are essential to the regeneration process, so we investigated the influence of human dental pulp stem cells (hDPSCs) on macrophage differentiation and the microenvironment and the underlying mechanism. Methods hDPSCs were isolated from healthy third molars extracted from patients undergoing maxillofacial surgery. The surface antigens CD73, CD45, CD90 and CD11b of the hDPSCs were detected using flow cytometry. hDPSCs were induced for osteogenic and adipogenic differentiation, and the outcome was assessed by alizarin red staining or Oil Red O staining. The IL-6 level released by hDPSCs was measured by enzyme linked immunosorbent assay (ELISA). Tohoku Hospital Pediatrics-1 (THP-1) cells were cultured and induced into macrophages by phorbol-12-myristate-13-acetate. After coculture of THP-1-derived macrophages with hDPSCs, interleukin 6 (IL-6), Argininase-1 (Arg-1), Mannose receptor C-1 (Mrc-1), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) levels in the medium were measured using ELISA and quantificational RT-PCR (qRT-PCR). The numbers of CD80 + and CD163 + macrophages were counted by immunofluorescence, and GP130/STAT3 signaling protein expression was detected. After coculturing the culture medium of hDPSCs with human bone marrow stem cells (BMSCs), scratch assays and transwell assays were performed to evaluate cell migration and invasion. Results Alkaline phosphatase (ALP) staining, alizarin red staining, and western blots were performed to assess osteoblast differentiation. The hDPSCs were positive for surface antigens CD73 and CD90 and negative for CD45 and CD11b expression. The level of IL-6 secreted by hDPSCs significantly increased the number of CD80 + cells as well as the levels of Arg-1 and Mrc-1. It also promoted M2 macrophage polarization and activated GP130/STAT3 signaling. However, the medium cocultured with THP-1-derived macrophages by hDPSCs facilitated the migration, invasion, and osteogenic abilities of human bone marrow-derived stem cells (hBMSCs). Conclusions hDPSCs can regulate the periodontal microenvironment through IL-6 by inducing phenotypic transformation of M2 macrophages and stimulating osteogenic differentiation of BMSCs.

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“…Keloids are benign skin fibroproliferative tumors unique to humans characterized by aggressive fibroblast proliferation, excessive accumulation of extracellular matrix (ECM) (e.g., collagen I and III), long-term continuous fibrosis, and abnormal inflammatory stimuli (Yan et al, 2021;Zhang et al, 2021). Keloids show various cancer-like features, such as aggressive proliferation beyond the original boundary, lack of spontaneous regression, and vascularization ability (Huang and Ogawa, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Circular RNA Expression in ceRNA Networks and Identification of the Effects of hsa_circ_0006867 in Keloid Dermal Fibroblasts

Pang

Lin

Sun

et al. 2022

Front. Mol. Biosci.

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Circular RNAs (circRNAs) play a crucial role in the pathogenesis of various fibrotic diseases, but the potential biological function and expression profile of circRNAs in keloids remain unknown. Herein, microarray technology was applied to detect circRNA expression in four patient-derived keloid dermal fibroblasts (KDFs) and normal dermal fibroblasts (NDFs). A total of 327 differentially expressed (DE) circRNAs (fold change > 1.5, p < 0.05) were identified with 195 upregulated and 132 downregulated circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the upregulated circRNAs were mainly enriched in the cytoskeleton and tight junctions, while the downregulated circRNAs were related to morphogenesis of the epithelium and axonal guidance. To explore the function of DE circRNAs, a circRNA-miRNA-mRNA network, including five circRNAs, nine miRNAs, and 235 correlated mRNAs, was constructed using bioinformatics analyses. The expression of five DE circRNAs was validated by qRT–PCR in 18 pairs of KDFs and NDFs, and hsa_circ_0006867 showed promising regulatory function in keloids in vitro. Silencing hsa_circ_00006867 suppressed the proliferation, migration, and invasion of keloid fibroblasts. RNA-binding protein immunoprecipitation (RIP) assays indicated that hsa_circ_00006867 may serve as a platform for miRNA binding to Argonaute (AGO) 2. In addition, hsa-miR-29a-5p may be a potential target miRNA of hsa_circ_00006867. Taken together, our research provided multiple novel clues to understand the pathophysiologic mechanism of keloids and identified hsa_circ_0006867 as a biomarker of keloids.

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Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts

Cited by 6 publications

References 33 publications

Characterization of Dental Pulp Stem Cell Populations in the Teeth of Patients With Neurofibromatosis Type 1 - Therapeutic Potential for Bone Tissue Engineering

Characterization of Dental Pulp Stem Cell Populations in the Teeth of Patients With Neurofibromatosis Type 1 - Therapeutic Potential for Bone Tissue Engineering

Dental pulp stem cells induce anti-inflammatory phenotypic transformation of macrophages to enhance osteogenic potential via IL-6/GP130/STAT3 signaling

Comprehensive Analysis of Circular RNA Expression in ceRNA Networks and Identification of the Effects of hsa_circ_0006867 in Keloid Dermal Fibroblasts

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