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Combinatorial Intervention with Mesenchymal Stem Cells and Granulocyte Colony-Stimulating Factor in a Rat Model of Ulcerative Colitis

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Abstract

Background

Bone marrow mesenchymal stem cells sometimes improve symptoms of inflammatory bowel disease.

Aim

To test the effects of combined granulocyte colony-stimulating factor (G-CSF) and MSC therapy in a rat model of ulcerative colitis (UC).

Methods

Seventy-two rats with TNBS-induced UC were divided into control or treatment groups: control (no disease and no treatment), no treatment (model), 5-aminosalicylate (5-ASA) enema, or MSCs (labeled with BrdU) with (MSC/GCSF) or without (MSC) G-CSF, and G-CSF alone (GCSF). On days 14 and 28 post-treatment, macroscopic and histological appearances were assessed and the disease activity index (DAI) scored to evaluate the severity of disease. BrdU-labeled MSCs were identified by immunofluorescence to confirm transplantation and their location. The inflammatory profile of each group was evaluated by measuring expression of nuclear NF-κB p65, serum TNF-α, and IL-10 and by activity of mucosal myeloperoxidase (MPO).

Results

Rats receiving MSC and G-CSF combination therapy had increased recruitment of MSCs to the colonic mucosa compared with rats receiving MSC transplantation alone. On day 28, the DAI, MPO activity, serum TNF-α and IL-10 levels, and NF-κB p65 expression in the combination therapy group were significantly lower compared to animals receiving no treatment, MSCs alone, or G-CSF alone (P < 0.05).

Conclusion

Intravenously transplanted MSCs migrate and distribute to the colon to effectively alleviate the symptoms of UC, while G-CSF enhances this effect via an anti-inflammatory effect and improvement in the pathologic features of UC. G-CSF may be a promising therapeutic regulator of MSCs that can improve therapeutic outcomes in patients with UC.

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Acknowledgments

This study was supported by Natural Science Foundation of Heilongjiang (D200826) and the Ministry of Science and Technology (2013CB967200).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China

    YinHua Tang, YingYing Chen, Xi Wang, Guang Song & LiJun Shi

  2. Department of Infection, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China

    YongGuo Li

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  1. YinHua Tang
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  2. YingYing Chen
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  3. Xi Wang
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  4. Guang Song
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Correspondence to YongGuo Li or LiJun Shi.

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Tang, Y., Chen, Y., Wang, X. et al. Combinatorial Intervention with Mesenchymal Stem Cells and Granulocyte Colony-Stimulating Factor in a Rat Model of Ulcerative Colitis. Dig Dis Sci 60, 1948–1957 (2015). https://doi.org/10.1007/s10620-015-3655-3

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  • DOI: https://doi.org/10.1007/s10620-015-3655-3

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