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

Bone marrow mesenchymal stem cells sometimes improve symptoms of inflammatory bowel disease. To test the effects of combined granulocyte colony-stimulating factor (G-CSF) and MSC therapy in a rat model of ulcerative colitis (UC). 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-kappa B p65, serum TNF-alpha, and IL-10 and by activity of mucosal myeloperoxidase (MPO). 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-alpha and IL-10 levels, and NF-kappa B 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). 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.