Abstract
BackgroundUlcerative 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.MethodsThe 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.ResultsImmunofluorescence 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-β 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-α and INF-γ) 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.ConclusionsThe 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.
Highlights
Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies
Compared with the control group, the body weights of the UC group were dramatically lower at day 14, and the disease activity index (DAI) scores showed the opposite trend (p < 0.01, Fig. 1f, g)
The rat-derived hepatocyte growth factor (HGF) gene was overexpressed in Dental pulp stem cells (DPSCs) by transduction of the lentiviral vector, and the therapeutic effects were explored in this study
Summary
Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) localized in the colon and rectum that is characterized by chronic and typically recurrent disease. IPAA is accompanied by significant trauma and a variety of related complications, such as wound infection, anastomotic leakage or stricture, small bowel obstruction, pelvic sepsis, pouch-related fistula, pouchitis and pouch failure [9,10,11]. These side effects impose an economic burden on patients and seriously affect their quality of life [12]. Novel therapies for UC are urgently required to improve the quality of life of patients
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