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.
Highlights
Inflammatory bowel disease (IBD) manifests as chronic inflammation of the colon and small intestine
The survival rate of colitis mice was significantly lower (~78% compared to the control) at the end of the experiment (Table 4), which was improved to that of the normal mice by treatment with tonsil-derived mesenchymal stem cells (TMSC)[x4]
Wellknown mesenchymal stem cells (MSC) isolated from bone marrow and adipose tissues have been tested to treat colitis due to their anti-inflammatory properties, a highly invasive procedure is required to obtain cells from adult donors
Summary
Inflammatory bowel disease (IBD) manifests as chronic inflammation of the colon and small intestine. MSC are capable of reducing the cells comprising a network of immune system such as dendritic cells, NK cells and T-cells [11,12,13], and of elevating secretion of anti-inflammatory cytokines such as interleukin 10 (IL-10) and prostaglandin E2 (PGE2) [14]. These findings suggest that IBD is a disease that could be effectively treated using MSC therapy [15, 16]. We reported that TMSC alleviate concanavalin A-induced acute hepatitis, indicating their role in the treatment of immune-mediated liver disease [27]
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