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.
Highlights
Inflammatory bowel disease (IBD) is a family of chronic inflammatory disorders of the gastrointestinal tract, which includes Crohn’s Disease (CD) and ulcerative colitis (UC), and is characterized by the dysfunction of T cells and uncontrolled production of inflammatory cytokines [1]
The currently available IBD treatments rely on immunosuppressive drugs and glucocorticoids but are not entirely effective, and remission often remains difficult to maintain [1,2]
As a novel IBD therapeutic approach, mesenchymal stem cells (MSCs) have emerged as potent regulators of the immune response [7,8,9], but little is known about their interaction with immunosuppressive drugs
Summary
Inflammatory bowel disease (IBD) is a family of chronic inflammatory disorders of the gastrointestinal tract, which includes Crohn’s Disease (CD) and ulcerative colitis (UC), and is characterized by the dysfunction of T cells and uncontrolled production of inflammatory cytokines [1]. The incidence of IBD has increased in pediatric patients, who present a history of multiple intestinal resections and immune modulating treatments with or without biological agents. Their response in the long term is uncertain, which is one of the many reasons why there is a search for new therapies and why mesenchymal stem cells are being looked to as one of the best options to treat these inflammatory conditions [3]
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