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.
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.
Authors: Claudia Veltkamp; Matthias Anstaett; Kristin Wahl; Sarah Möller; Saskia Gangl; Oliver Bachmann; Matthias Hardtke-Wolenski; Florian Länger; Wolfgang Stremmel; Michael P Manns; Klaus Schulze-Osthoff; Heike Bantel Journal: Gut Date: 2011-04-01 Impact factor: 23.059
Authors: Xochitl C Morgan; Timothy L Tickle; Harry Sokol; Dirk Gevers; Kathryn L Devaney; Doyle V Ward; Joshua A Reyes; Samir A Shah; Neal LeLeiko; Scott B Snapper; Athos Bousvaros; Joshua Korzenik; Bruce E Sands; Ramnik J Xavier; Curtis Huttenhower Journal: Genome Biol Date: 2012-04-16 Impact factor: 13.583
Authors: Fausto Sánchez-Muñoz; Gabriela Fonseca-Camarillo; Marco A Villeda-Ramírez; Elizabeth Miranda-Pérez; Edgar J Mendivil; Rafael Barreto-Zúñiga; Misael Uribe; Rafael Bojalil; Aarón Domínguez-López; Jesús K Yamamoto-Furusho Journal: BMC Gastroenterol Date: 2011-12-20 Impact factor: 3.067