Mesenchymal stromal cell function is not affected by drugs used in the treatment of inflammatory bowel disease

• Published in: Cytotherapy (Oxford, England) England), 2011-10, Vol.13 (9), p.1066-1073
• Main Authors: Duijvestein, Marjolijn, Molendijk, Ilse, Roelofs, Helene, Vos, Anne Christine W, Verhaar, Auke P, Reinders, Marlies E.J, Fibbe, Willem E, Verspaget, Hein W, van den Brink, Gijs R, Wildenberg, Manon E, Hommes, Daniel W
• Format: Article
• Language: English
• Subjects: Adipogenesis - drug effects; Advanced Basic Science; anti-tumor necrosis factor-α; Antibodies, Monoclonal - pharmacology; Azathioprine - pharmacology; Cell Differentiation - drug effects; Cell Survival - drug effects; Cells, Cultured; Combined Modality Therapy; Crohn's disease; Humans; Immune Tolerance - drug effects; immunomodulators; Immunosuppression - adverse effects; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - pathology; Inflammatory Bowel Diseases - physiopathology; medication; Mercaptopurine - pharmacology; mesenchymal stromal cell; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Methotrexate - pharmacology; Osteogenesis - drug effects; Other; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - drug effects; Pluripotent Stem Cells - metabolism; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - immunology
• ISSN: 1465-3249; 1477-2566
• DOI: 10.3109/14653249.2011.597379

Abstract Background and aims Mesenchymal stromal cells (MSC) have both multilineage differentiation capacity and immunosuppressive properties. Promising results with MSC administration have been obtained in experimental colitis. Clinical application of MSC for the treatment of inflammatory bowel disease (IBD) is currently under investigation in phase I–III trials in patients with past or concurrent immunomodulating therapy. However, little is known about MSC interactions with these immunosuppressive drugs. To address this issue we studied the combined effect of MSC and IBD drugs in in vitro functionality assays Methods The effects of azathioprine, methotrexate, 6-mercaptopurine and anti-tumor necrosis factor (TNF)-α on MSC phenotype, survival, differentiation capacity and immunosuppressive capacity were studied Results MSC exposed to physiologically relevant concentrations of IBD drugs displayed a normal morphology and fulfilled phenotypic and functional criteria for MSC. Differentiation into adipocyte and osteocyte lineages was not affected and cells exhibited normal survival after exposure to the various drugs. MSC suppression of peripheral blood mononuclear cell (PBMC) proliferation in vitro was not hampered by IBD drugs. In fact, in the presence of 6-mercaptopurine and anti-TNF-α antibodies, the inhibitory effect of this drug alone was enhanced, suggesting an additive effect of pharmacotherapy and MSC treatment Conclusions This study demonstrates that, in vitro , MSC phenotype and function are not affected by therapeutic concentrations of drugs commonly used in the treatment of IBD. These findings are important for the potential clinical use of MSC in combination with immunomodulating drugs and anti-TNF-α therapy.