title: Adipose mesenchymal stromal cell function is not affected by methotrexate and azathioprine.
abstract: Given their capacity to modulate the immune response, adipose mesenchymal stem or stromal cells (ASCs) have been used as therapeutic tools to treat chronic inflammatory and autoimmune diseases both in preclinical and clinical studies. Patients enrolled in such clinical trials are often concomitantly treated with immunomodulatory drugs such as methotrexate (MTX) or azathioprine (AZA). Therefore it is necessary to investigate the possible impact of these drugs on ASC function to learn if there are any interactions that would affect the therapeutic effects of either component and thus the clinical outcome of the trials. ASCs were cultured in the absence or presence of MTX or AZA and the effects on viability, proliferation, immunomodulatory properties, and immunogenic features were studied in vitro. The drugs did not affect the viability and proliferative capacity of ASCs. When the drugs and the ASCs were concomitantly used to inhibit lymphocyte proliferation, no synergistic or antagonizing inhibitory effects were found. MTX and AZA did not impair the capacity of ASCs to induce the generation of regulatory T cells in vitro. These data confirm that the immunomodulating features of ASCs are fully functional after exposure to these drugs. Interestingly, whereas MTX did not affect the capacity of natural killer (NK) cells to lyse allogeneic ASCs in vitro, AZA protected allogeneic ASCs from NK cell lysis.
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Pablo
authors.initials: P
authors.lastname: Mancheño-Corvo
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center , Rotterdam, The Netherlands .
authors.forename: Marcella
authors.initials: M
authors.lastname: Franquesa
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Olga
authors.initials: O
authors.lastname: de la Rosa
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramírez
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Leyre
authors.initials: L
authors.lastname: García-Benzaquén
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fernández
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Ramón
authors.initials: R
authors.lastname: Menta
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Aitor
authors.initials: A
authors.lastname: Beraza
authors.affiliation: TiGenix NV , Leuven, Belgium .
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center , Rotterdam, The Netherlands .
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.affiliation: TiGenix SAU , Madrid, Spain .
authors.forename: Eleuterio
authors.initials: E
authors.lastname: Lombardo
keywords: azathioprine; cell therapy; mesenchymal stem cells; methotrexate