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Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
Therapeutic potential of tonsil-derived mesenchymal stem cells in dextran sulfate sodium-induced experimental murine
Yeonsil Yu1, Eun Mi Song2, Ko Eun Lee2
1Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, South Korea.
Abstract:
The therapeutic potential of tonsil-derived mesenchymal stem cells (TMSC) prepared from human tonsillar tissue has been studied in animal models for several diseases such as hepatic injury, hypoparathyroidism, diabetes and muscle dystrophy. In this study, we examined the therapeutic effects of TMSC in a dextran sulfate sodium (DSS)-induced colitis model. TMSC were injected in DSS-induced colitis mice via intraperitoneal injection twice (TMSC[x2]) or four times (TMSC[x4]). Control mice were injected with either phosphate-buffered saline or human embryonic kidney 293 cells. Body weight, stool condition and disease activity index (DAI) were examined daily. Colon length, histologic grading, and mRNA expression of pro-inflammatory cytokines, interleukin 1β (IL-1β), IL-6, IL-17 and tumor necrosis factor α, and anti-inflammatory cytokines, IL-10, IL-11 and IL-13, were also measured. Our results showed a significant improvement in survival rates and body weight gain in colitis mice injected with TMSC[x2] or TMSC[x4]. Injection with TMSC also significantly decreased DAI scores throughout the experimental period; at the end of experiment, almost complete reversal of DAI scores to normal was found in colitis mice treated with TMSC[x4]. Colon length was also significantly recovered in colitis mice treated with TMSC[x4]. However, histopathological alterations induced by DSS treatment were not apparently improved by injection with TMSC. Finally, treatment with TMSC[x4] significantly reversed the mRNA levels of IL-1β and IL-6, although expression of all pro-inflammatory cytokines tested was induced in colitis mice. Under our experimental conditions, however, no apparent alterations in the mRNA levels of all the anti-inflammatory cytokines tested were found. In conclusion, our findings demonstrate that multiple injections with TMSC produced a therapeutic effect in a mouse model of DSS-induced colitis.
Insights
Multiple injections of tonsil-derived mesenchymal stem cells (TMSC) significantly improved survival and reduced disease activity in a mouse model of dextran sulfate sodium (DSS)-induced colitis. TMSC therapy offers therapeutic potential for inflammatory bowel disease.
Area of Science:
- Immunology
- Regenerative Medicine
- Gastroenterology
Background:
- Tonsil-derived mesenchymal stem cells (TMSC) show therapeutic promise in preclinical models for various diseases.
- Inflammatory bowel disease, such as colitis, is characterized by chronic inflammation and tissue damage in the gastrointestinal tract.
- Mesenchymal stem cells are being investigated for their immunomodulatory and regenerative properties in treating inflammatory conditions.
Purpose of the Study:
- To evaluate the therapeutic efficacy of TMSC in a dextran sulfate sodium (DSS)-induced mouse model of colitis.
- To assess the impact of TMSC treatment on clinical signs, colon length, and inflammatory cytokine expression in colitis.
Main Methods:
- Mice were induced with colitis using DSS and treated with phosphate-buffered saline, human embryonic kidney 293 cells, or TMSC via intraperitoneal injection twice (TMSC[x2]) or four times (TMSC[x4]).
- Clinical parameters including body weight, stool condition, and disease activity index (DAI) were monitored daily.
- Colon length, histopathology, and mRNA expression of pro- and anti-inflammatory cytokines (IL-1β, IL-6, IL-17, TNF-α, IL-10, IL-11, IL-13) were analyzed post-treatment.
Main Results:
- TMSC treatment significantly improved survival rates and body weight gain in DSS-induced colitis mice.
- Multiple TMSC injections (TMSC[x2] and TMSC[x4]) led to a significant decrease in DAI scores, with near-complete reversal in the TMSC[x4] group.
- TMSC[x4] treatment significantly recovered colon length and reversed mRNA levels of IL-1β and IL-6, but did not significantly alter histopathological findings or anti-inflammatory cytokine expression.
Conclusions:
- Multiple administrations of TMSC demonstrate significant therapeutic effects in a mouse model of DSS-induced colitis.
- TMSC treatment effectively ameliorates clinical symptoms and reduces key pro-inflammatory cytokine expression in colitis.
- Further research is warranted to optimize TMSC dosage and delivery for potential clinical application in inflammatory bowel disease.
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