title: Mesenchymal stromal cell function is not affected by drugs used in the treatment of inflammatory bowel disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University, Medical Center, Leiden, the Netherlands. m.duijvestein@lumc.nl
authors.forename: Marjolijn
authors.initials: M
authors.lastname: Duijvestein
authors.forename: Ilse
authors.initials: I
authors.lastname: Molendijk
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.forename: Anne Christine W
authors.initials: AC
authors.lastname: Vos
authors.forename: Auke P
authors.initials: AP
authors.lastname: Verhaar
authors.forename: Marlies E J
authors.initials: ME
authors.lastname: Reinders
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Hein W
authors.initials: HW
authors.lastname: Verspaget
authors.forename: Gijs R
authors.initials: GR
authors.lastname: van den Brink
authors.forename: Manon E
authors.initials: ME
authors.lastname: Wildenberg
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001379:Azathioprine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000009:adverse effects; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015122:Mercaptopurine / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D015122:Mercaptopurine; D001379:Azathioprine; D008727:Methotrexate