Additional file 1 of Genome-wide identification of long noncoding RNAs and their competing endogenous RNA networks involved in the odontogenic differentiation of human dental pulp stem cells
0
Citation
0
Reference
10
Related Paper
Abstract:
Additional file 1: Table S1. The expression profiles of upregulated lncRNAs in differentiated and undifferentiated hDPSCs. (XLS 72 kb)Primary cell
Cite
Citations (3)
Abstract Stem cells isolated from patients with rare diseases are important to elucidate their pathogeny and mechanisms to enable regenerative therapy. However, the mechanisms underlying tissue regeneration using patient‐derived dental pulp stem cells (DPSCs) are unclear. In this study, we investigated the levels of mRNA and protein expression related to cellular differentiation of Crouzon syndrome patient‐derived DPSCs (CS‐DPSCs) with a Gly338Arg fibroblast growth factor receptor 2 mutation. Multipotency‐related gene expression levels were equivalent in both healthy donor DPSCs and CS‐DPSCs. CS‐DPSCs showed higher osteocalcin ( OCN ) expression than healthy donor DPSCs. CS‐DPSCs showed a lower increase in the rate of OCN expression among phorbol 12‐myristate 13‐acetate (PMA)‐treated cells than healthy donor DPSCs compared with untreated control cells. CS‐DPSCs showed a lower phosphorylation rate of p38 and p44/42 in PMA‐treated cells than healthy donor DPSCs compared with untreated control cells. These results demonstrate that CS‐DPSCs have higher OCN expression and lower PMA stimulation‐responsiveness than healthy donor DPSCs.
Cite
Citations (1)
Cite
Citations (10)
Cite
Citations (63)
Cite
Citations (23)
Cite
Citations (61)
Abstract Background Dental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. We have demonstrated the safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. The device for isolation of MDPSCs, however, is not cost-effective and requires a prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSC proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry. Methods Colony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity, and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ was investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of the blood and urine tests. Results hpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α , and a stem cell marker, CXCR-4 . The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration, and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly upregulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation. Conclusions These results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.
Regenerative Medicine
Stem Cell Therapy
Cite
Citations (34)
To investigate the characteristics and molecular events of dental pulp stem cells (DPSCs) for tissue regeneration with aging, we isolated and analyzed the stem cells from human exfoliated deciduous teeth (SHED) and permanent teeth of young (Y-DPSCs) and old (A-DPSCs) adults. Results showed that the stemness and osteogenic differentiation capacity of DPSCs decreased with aging. The RNA sequencing results showed that glycine, serine, and threonine metabolism was one of the most enriched gene clusters among SHED, Y-DPSCs, and A-DPSCs, according to analysis based on the Kyoto Encyclopedia of Genes and Genomes. The expression of serine metabolism-related enzymes phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate (PHGDH) decreased in A-DPSCs and provided less methyl donor S-adenosylmethionine (SAM) for DNA methylation, leading to the hypomethylation of the senescence marker p16 (CDNK2A). Furthermore, the proliferation and differentiation capacity of Y-DPSCs and SHED decreased after PHGDH siRNA treatment, which reduced the level of SAM. Convincingly, the ratios of PSAT1-, PHGDH-, or proliferating cell nuclear antigen-positive cells in the dental pulp of old permanent teeth were less than those in the dental pulp of deciduous teeth and young permanent teeth. In summary, the stemness and differentiation capacity of DPSCs decreased with aging. The decreased serine metabolism in A-DPSCs upregulated the expression of p16 via attenuating its DNA methylation, resulting in DPSC aging. Our finding indicated that serine metabolism and 1 carbon unit participated in stem cell aging, which provided new direction for stem cell aging study and intervention.
Dentinogenesis
Cite
Citations (30)
The aim of the present study was to assess the influence of metformin on the angiogenic ability of secretomes from dental pulp stem cells. The stem cells were obtained from the dental pulp (DPSCs) (n = 3) using the explant culture method. We treated the DPSCs with different concentrations of metformin and assessed the expression of the angiogenesis-related genes. We also tested the angiogenic effect of the secretomes on the yolk sac membrane of the chick embryos by counting the quaternary blood vessel formations on the yolk sac membrane. We found that metformin treatment enhanced the angiogenic potential of the stem cell secretome in a dose-dependent manner. This was evidenced by the increase in the quaternary blood vessel formations in the yolk sac membrane with lower to higher concentrations of metformin. Pre-treatment with metformin modulates the angiogenic potential of the stem cell-conditioned media in a dose-dependent manner. The augmentation of the angiogenic potential of the DPSCs can aid regeneration, especially in scenarios requiring the regeneration of vacuoles.
Cite
Citations (6)
To isolate,culture and identify human dental pulp stem cells(hDPSCs) and investigate the expression of exogenous in hDPSCs.DPSCs were transduced with EGFP by lentiviral vector.The effect of infection on proliferation of DPSCs was evaluated by MTT.Approximately 5×106 of DPSCs (third passage) were mixed with 40 mg of HA/TCP ceramic powder and then transplanted s.c.into the dorsal surface of 10-week-old immunocompromised beige mice.Results indicates: EGFP was stably introduced to DPSCs by lentiviral vector.The infection had no significant effect on the proliferation of DPSCs.After 8 weeks posttransplantation,DPSCs which infected EGFP generated a dentin-like structure lining the surfaces of the HA/TCP particles.Exogenous can be stably expressed in hDPSC mediated by lentiviral vector.And EGFP can be use for labeling gene in the lentiviral vector.
Cite
Citations (0)