Dataset Information

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis.

ABSTRACT:

Background

Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Dental pulp stem cell (DPSC) transplantation has been proposed as a potential therapy for UC. This study aimed to investigate the therapeutic effects of the rat hepatocyte growth factor (HGF) gene transduced into DPSCs for UC.

Methods

The therapeutic effects of HGF-DPSCs transplanted intravenously into a rat model of UC induced by 5% dextran sulphate sodium (DSS) were compared with the other treatment groups (LV-HGF group, DPSCs group and GFP-DPSCs group). Immunofluorescence and immunohistochemistry were used to observe the localization and proliferation of HGF-DPSCs at the site of colon injury. The expression levels of inflammatory factors were detected by real-time quantitative PCR (RT-PCR) and western blotting. The oxidative stress markers were detected by ELISA. DAI scores and body weight changes were used to macroscopically evaluate the treatment of rats in each group.

Results

Immunofluorescence and immunohistochemistry assays showed that HGF-DPSCs homed to colon injury sites and colocalized with intestinal stem cell (ISC) markers (Bmi1, Musashi1 and Sox9) and significantly promoted protein expression (Bmi1, Musashi1, Sox9 and PCNA). Anti-inflammatory cytokine (TGF-? and IL-10) expression was the highest in the HGF-DPSCs group compared with the other treatment groups, while the expression of pro-inflammatory cytokines (TNF-? and INF-?) was the lowest. Additionally, the oxidative stress response results showed that malondialdehyde (MDA) and myeloperoxidase (MPO) expression decreased while superoxide dismutase (SOD) expression increased, especially in the HGF-DPSCs group. The DAI scores showed a downward trend with time in the five treatment groups, whereas body weight increased, and the changes were most prominent in the HGF-DPSCs group.

Conclusions

The study indicated that HGF-DPSCs can alleviate injuries to the intestinal mucosa by transdifferentiating into ISC-like cells, promoting ISC-like cell proliferation, suppressing inflammatory responses and reducing oxidative stress damage, which provides new ideas for the clinical treatment of UC.

SUBMITTER: Li N

PROVIDER: S-EPMC7792189 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis.

Li Ning N Zhang Yichi Y Nepal Narayan N Li Guoqing G Yang Ningning N Chen Haoyuan H Lin Qiuchi Q Ji Xuechun X Zhang Sijia S Jin Shizhu S

Stem cell research & therapy 20210107 1

<h4>Background</h4>Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Dental pulp stem cell (DPSC) transplantation has been proposed as a potential therapy for UC. This study aimed to investigate the therapeutic effects of the rat hepatocyte growth factor (HGF) gene transduced into DPSCs for UC.<h4>Methods</h4>The therapeutic effects of HGF-DPSCs transplanted intravenously into a rat model of UC induced by 5% dextran sulphate sodium (DSS) were c ...[more]

PMID: 33413675

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Project description:AimsThe potential signaling pathways and core genes in ulcerative colitis (UC) were investigated in this study. Furthermore, potential mechanisms of BBR in treating UC were also explored.MethodsExpression profiling by array of UC patients were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were determined with the differential analysis. The biological functions of DEGs were analyzed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Gene Set Enrichment Analysis (GSEA) was applied to analyze the expression differences between two different phenotype sample sets. Dextran sulfate sodium (DSS) was applied to establish UC model of mice and lipopolysaccharide (LPS) was utilized to induce inflammatory damage of NCM460 cells. Therapeutic effects of berberine (BBR) on disease performance, pathologic changes and serum supernatant indices were analyzed in vivo. To further investigate the potential mechanisms of BBR in treating UC, the expression of genes and proteins in vivo and in vitro were examined by RT-qPCR, immunohistochemical staining and western blotting.ResultsImmune-inflammatory genes were identified and up-regulated significantly in UC patients. In addition, IFN-γ signaling pathway and its core genes were significantly up-regulated in the phenotype of UC. All disease performance and the pathologic changes of UC in mice were evidently ameliorated by BBR treatment. The pro-inflammatory cytokines of serum, including CXCL9, CXCL1, IL-17 and TNF-α, in UC mice were significantly reduced by treatment of BBR. In terms of mechanisms of BBR in treating UC, the pro-inflammatory and immune-related genes, encoding IFN-γ, IRF8, NF-κB and TNF-α decreased significantly in UC mice followed by BBR treatment. Meanwhile, the expression of IFN-γ and its initiated targets, including IRF8, Ifit1, Ifit3, IRF1, were suppressed significantly by BBR treatment in vivo. The blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Furthermore, the blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR.ConclusionBBR holds anti-inflammatory activity and can treat UC effectively. The anti-inflammatory property of BBR is tightly related to the suppression of IFN-γ signaling pathway, which is crucial in immune-inflammatory responses of the colon mucosa.

Project description:BackgroundDental 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.MethodsColony-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.ResultshpDPSCs 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.ConclusionsThese 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.

Dataset Information

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis.

Background

Methods

Results

Conclusions

Publications

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis.

Similar Datasets

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