title: Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior.
abstract: Glucocorticoids and immunosuppressive drugs are commonly used to treat inflammatory disorders, such as inflammatory bowel disease (IBD), and despite a few improvements, the remission of IBD is still difficult to maintain. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have emerged as regulators of the immune response, and their viability and activation of their migratory properties are essential for successful cell therapy. However, little is known about the effects of immunosuppressant drugs used in IBD treatment on MSC behavior. The aim of this study was to evaluate MSC viability, nuclear morphometry, cell polarity, F-actin and focal adhesion kinase (FAK) distribution, and cell migratory properties in the presence of the immunosuppressive drugs azathioprine (AZA) and dexamethasone (DEX). After an initial characterization, MSCs were treated with DEX (10 μM) or AZA (1 μM) for 24 hrs or 7 days. Neither drug had an effect on cell viability or nuclear morphometry. However, AZA treatment induced a more elongated cell shape, while DEX was associated with a more rounded cell shape (P < 0.05) with a higher presence of ventral actin stress fibers (P < 0.05) and a decrease in protrusion stability. After 7 days of treatment, AZA improved the cell spatial trajectory (ST) and increased the migration speed (24.35%, P < 0.05, n = 4), while DEX impaired ST and migration speed after 24 hrs and 7 days of treatment (-28.69% and -25.37%, respectively; P < 0.05, n = 4). In conclusion, our data suggest that these immunosuppressive drugs each affect MSC morphology and migratory capacity differently, possibly impacting the success of cell therapy.
authors.affiliation: Embryology and Cell Differentiation Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil; Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos 2400, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Schneider
authors.affiliation: Embryology and Cell Differentiation Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil; Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos 2400, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Fabiany da Costa
authors.initials: Fda C
authors.lastname: Gonçalves
authors.affiliation: Embryology and Cell Differentiation Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Fernanda Otesbelgue
authors.initials: FO
authors.lastname: Pinto
authors.affiliation: Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Patrícia Luciana da Costa
authors.initials: PL
authors.lastname: Lopez
authors.affiliation: Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Anelise Bergmann
authors.initials: AB
authors.lastname: Araújo
authors.affiliation: Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Pfaffenseller
authors.affiliation: Embryology and Cell Differentiation Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Eduardo Pandolfi
authors.initials: EP
authors.lastname: Passos
authors.affiliation: Embryology and Cell Differentiation Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Elizabeth Obino
authors.initials: EO
authors.lastname: Cirne-Lima
authors.affiliation: Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos 2400, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Luíse
authors.initials: L
authors.lastname: Meurer
authors.affiliation: Morphological Sciences Department, Health Basic Sciences Institute, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, CEP 90050-170, Porto Alegre, RS, Brazil.
authors.forename: Marcelo Lazzaron
authors.initials: ML
authors.lastname: Lamers
authors.affiliation: Embryology and Cell Differentiation Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, CEP 90035-903, Porto Alegre, RS, Brazil; Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos 2400, CEP 90035-903, Porto Alegre, RS, Brazil; Morphological Sciences Department, Health Basic Sciences Institute, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, CEP 90050-170, Porto Alegre, RS, Brazil.
authors.forename: Ana Helena
authors.initials: AH
authors.lastname: Paz
mesh_terms: D001379:Azathioprine / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*
chemical_list: D007166:Immunosuppressive Agents; D003907:Dexamethasone; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D001379:Azathioprine