J Korean Surg Soc.  2010 Nov;79(5):317-325. 10.4174/jkss.2010.79.5.317.

Immunomodulatory Effects of Mesenchymal Stem Cells in a Murine Model of TNBS-Induced Colitis

• Cho YB
• Kim MS
• Kang MJ
• Shin HJ
• Kim SH
• Kim HC
• Yun SH
• Lee WY
• Chun HK

• KMID: 2212035
• DOI: http://doi.org/10.4174/jkss.2010.79.5.317

Abstract

PURPOSE
Mesenchymal stem cells (MSCs) are surfacing as a new method of treatment for various diseases that have poor outcome with drug treatments. In this study, we investigated the effects of MSCs in a murine intestinal inflammation model mimicking human Crohn's disease (CD) using 2,4,5-trinitrobenzene sulfonic acid (TNBS).
METHODS
Colitis was induced by rectal administration of 2 mg of TNBS in 35% ethanol as experimental group compared to control group. Histological changes, surface molecules of T and B cells of the spleen and blood, and cytokine production (IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, and IL-12) were determined among 3 groups comprised of control group, TNBS group and TNBS/MSC group.
RESULTS
In the mice treated with MSCs, there was a decrease in the wasting disease process and inflammatory histopathological changes. There was also a decrease in pro-inflammatory T-helper 1 (Th1) cytokines IFN-gamma and IL-12 and T-helper 2 (Th2) cytokine IL-4. Anti-inflammatory cytokine IL-10 increased in mice treated with MSCs compared to colitic mice. The blood CD4+CD25+ T-regulatory cells also increased and splenic CD19 B-cells decreased.
CONCLUSION
The results of this study suggest that MSCs may have a therapeutic effect in controlling the Th1 and Th2 mediated immune response in patients with CD and aid in tissue regeneration.

Keyword

Mesenchymal stem cell; Inflammatory bowel disease; Crohn's disease

MeSH Terms

Administration, Rectal
Animals
B-Lymphocytes
Colitis
Crohn Disease
Cytokines
Ethanol
Humans
Inflammation
Inflammatory Bowel Diseases
Interleukin-10
Interleukin-12
Interleukin-4
Interleukin-6
Mesenchymal Stromal Cells
Mice
Regeneration
Spleen
Tumor Necrosis Factor-alpha
Wasting Syndrome
Cytokines
Ethanol
Interleukin-10
Interleukin-12
Interleukin-4
Interleukin-6
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Survival rate and body weight after induction of TNBS colitis. Survival rate after induction of TNBS colitis in mice treated with MSC. Application of MSC caused a significant decrease in mortality rates in TNBS colitis. The graph represents data from six independent experiments with at least ten mice in each group.

• 

  Fig. 2 TNBS colitis and influence of MSC on body weight. Body weight was recorded daily from days 1 to 10. The change in weight is expressed as the percentage of body weight from day 1. Administration of MSC reduced weight loss in TNBS colitis. Results are representative of six experiments.

• 

  Fig. 3 Histological analysis of colonic specimens on day 3 and 10 after induction of TNBS colitis. (A) Control/Et-OH mice post-op day 3 (A-1) and day 10 (A-2), respectively. (B) TNBS colitis induced mice post-op day 3 (B-1) and day 10 (B-2), respectively. (C) TNBS colitis induced mice treated with MSCs post-op day 3 (C-1) and day 10 (C-2). Treatment with MSCs led to reduction in TNBS-induced inflammation. Significantly less inflammation, fewer cell infiltration and crypt destruction were present in MSC treated colitic mice (C) compared with TNBS colitic mice (B).

• 

  Fig. 4 Effect of MSC treatment on cytokine production. The results are representative of six experiments. *P<0.05.

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