Testing Stem Cell Therapy in a Rat Model of Inflammatory Bowel Disease: Role of Bone Marrow Stem Cells and Stem Cell Factor in Mucosal Regeneration |
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Authors: | Bo Qu Guo-Rong Xin Li-Xia Zhao Hui Xing Li-Ying Lian Hai-Yan Jiang Jia-Zhao Tong Bei-Bei Wang Shi-Zhu Jin |
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Affiliation: | 1. Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.; 2. Anorectal Department, The First Affiliated Hospital, JiaMuSi Medical University, JiaMuSi, China.; 3. Infections Department, JiaMuSi Central Hospital, JiaMuSi, China.; University Claude Bernard Lyon 1, France, |
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Abstract: | BackgroundThe gastrointestinal (GI) mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs) and soluble stem cell factor (SCF) in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD).MethodsBMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls.ResultsPKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA), Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group.ConclusionBMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD. |
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