Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior
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 e...
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creator | Schneider, Natália Gonçalves, Fabiany da Costa Pinto, Fernanda Otesbelgue Lopez, Patrícia Luciana da Costa Araújo, Anelise Bergmann Pfaffenseller, Bianca Passos, Eduardo Pandolfi Cirne-Lima, Elizabeth Obino Meurer, Luíse Lamers, Marcelo Lazzaron Paz, Ana Helena |
description | 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. |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0120538</identifier><identifier>PMID: 25756665</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actin ; Adhesion tests ; Azathioprine ; Azathioprine - pharmacology ; Bone marrow ; Care and treatment ; Cell adhesion & migration ; Cell migration ; Cell Movement - drug effects ; Cell Shape - drug effects ; Cell size ; Cell Survival ; Cells, Cultured ; Cytokines ; Cytology ; Cytoskeleton ; Cytoskeleton - metabolism ; Dexamethasone ; Dexamethasone - pharmacology ; Dosage and administration ; Drug Evaluation, Preclinical ; Drugs ; Elongation ; Embryology ; Fibers ; Focal adhesion kinase ; Focal Adhesion Kinase 1 - metabolism ; Gastroenterology ; Gastrointestinal diseases ; Glucocorticoids ; Hepatology ; Humans ; Immune response ; Immune system ; Immunomodulation ; Immunosuppressive agents ; Immunosuppressive Agents - pharmacology ; Inflammation ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Inflammatory diseases ; Intestine ; Kinases ; Laboratories ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - physiology ; Mesenchyme ; Morphology ; Morphometry ; Physiological aspects ; Polarity ; Properties (attributes) ; Regulators ; Remission ; Signal transduction ; Spatial distribution ; Stem cells ; Steroids ; Therapy</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0120538-e0120538</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Schneider et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Schneider et al 2015 Schneider et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-176b713e39cb2553032b407dc05af8d2047780e81d2f69fb6444f0a3f37b74283</citedby><cites>FETCH-LOGICAL-c758t-176b713e39cb2553032b407dc05af8d2047780e81d2f69fb6444f0a3f37b74283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355407/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355407/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25756665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Genetos, Damian Christopher</contributor><creatorcontrib>Schneider, Natália</creatorcontrib><creatorcontrib>Gonçalves, Fabiany da Costa</creatorcontrib><creatorcontrib>Pinto, Fernanda Otesbelgue</creatorcontrib><creatorcontrib>Lopez, Patrícia Luciana da Costa</creatorcontrib><creatorcontrib>Araújo, Anelise Bergmann</creatorcontrib><creatorcontrib>Pfaffenseller, Bianca</creatorcontrib><creatorcontrib>Passos, Eduardo Pandolfi</creatorcontrib><creatorcontrib>Cirne-Lima, Elizabeth Obino</creatorcontrib><creatorcontrib>Meurer, Luíse</creatorcontrib><creatorcontrib>Lamers, Marcelo Lazzaron</creatorcontrib><creatorcontrib>Paz, Ana Helena</creatorcontrib><title>Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Actin</subject><subject>Adhesion tests</subject><subject>Azathioprine</subject><subject>Azathioprine - pharmacology</subject><subject>Bone marrow</subject><subject>Care and treatment</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cell Shape - drug effects</subject><subject>Cell size</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Cytology</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - metabolism</subject><subject>Dexamethasone</subject><subject>Dexamethasone - pharmacology</subject><subject>Dosage and administration</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drugs</subject><subject>Elongation</subject><subject>Embryology</subject><subject>Fibers</subject><subject>Focal adhesion kinase</subject><subject>Focal Adhesion Kinase 1 - metabolism</subject><subject>Gastroenterology</subject><subject>Gastrointestinal diseases</subject><subject>Glucocorticoids</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunomodulation</subject><subject>Immunosuppressive agents</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Inflammatory diseases</subject><subject>Intestine</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - physiology</subject><subject>Mesenchyme</subject><subject>Morphology</subject><subject>Morphometry</subject><subject>Physiological aspects</subject><subject>Polarity</subject><subject>Properties (attributes)</subject><subject>Regulators</subject><subject>Remission</subject><subject>Signal transduction</subject><subject>Spatial distribution</subject><subject>Stem cells</subject><subject>Steroids</subject><subject>Therapy</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0tv1DAQxyMEoqXwDRBEQkJw2MWP-JELUlVeK1WqxOtqOc54k5LEi-2tunx6nG5abVAPyAdbM7_5j2fsybLnGC0xFfjdpdv6QXfLjRtgiTBBjMoH2TEuKVlwgujDg_NR9iSESzQinD_OjggTjHPOjjP3Aa51D7HRIenkeqhz_UfHpnUb3ybDxrveRcjNLrrwCzqIustNo4c1hD1tLZiY9xBgMM2uT-4Qoc8NdF3et2uvo_O7vIJGX7XOP80eWd0FeDbtJ9mPTx-_n31ZnF98Xp2dni-MYDIusOCVwBRoaSrCGEWUVAUStUFMW1kTVAghEUhcE8tLW_GiKCzS1FJRiYJIepK93OtuOhfU1KugMOe4lILyIhGrPVE7falStb32O-V0q24Mzq-V9rE1HShsDCtLK1EFtgAuZQ2yYmDLKqUmXCSt91O2bdVDbWCIXncz0blnaBu1dleqoIylupLAm0nAu99bCFH1bRhbqAdw25t7E06FLHFCX_2D3l_dRK11KqAdrEt5zSiqTgvCmeSSjGmX91Bp1dC3Jn0I2yb7LODtLCAxEa7jWm9DUKtvX_-fvfg5Z18fsA3oLjbBddvYuiHMwWIPGu9C8GDvmoyRGufithtqnAs1zUUKe3H4QHdBt4NA_wK4twnc</recordid><startdate>20150310</startdate><enddate>20150310</enddate><creator>Schneider, 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and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior</title><author>Schneider, Natália ; Gonçalves, Fabiany da Costa ; Pinto, Fernanda Otesbelgue ; Lopez, Patrícia Luciana da Costa ; Araújo, Anelise Bergmann ; Pfaffenseller, Bianca ; Passos, Eduardo Pandolfi ; Cirne-Lima, Elizabeth Obino ; Meurer, Luíse ; Lamers, Marcelo Lazzaron ; Paz, Ana Helena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-176b713e39cb2553032b407dc05af8d2047780e81d2f69fb6444f0a3f37b74283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Actin</topic><topic>Adhesion tests</topic><topic>Azathioprine</topic><topic>Azathioprine - pharmacology</topic><topic>Bone marrow</topic><topic>Care and treatment</topic><topic>Cell adhesion & migration</topic><topic>Cell migration</topic><topic>Cell Movement - drug effects</topic><topic>Cell Shape - drug effects</topic><topic>Cell size</topic><topic>Cell Survival</topic><topic>Cells, Cultured</topic><topic>Cytokines</topic><topic>Cytology</topic><topic>Cytoskeleton</topic><topic>Cytoskeleton - metabolism</topic><topic>Dexamethasone</topic><topic>Dexamethasone - pharmacology</topic><topic>Dosage and administration</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drugs</topic><topic>Elongation</topic><topic>Embryology</topic><topic>Fibers</topic><topic>Focal adhesion kinase</topic><topic>Focal Adhesion Kinase 1 - metabolism</topic><topic>Gastroenterology</topic><topic>Gastrointestinal diseases</topic><topic>Glucocorticoids</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunomodulation</topic><topic>Immunosuppressive agents</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Inflammation</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>Inflammatory diseases</topic><topic>Intestine</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - physiology</topic><topic>Mesenchyme</topic><topic>Morphology</topic><topic>Morphometry</topic><topic>Physiological aspects</topic><topic>Polarity</topic><topic>Properties (attributes)</topic><topic>Regulators</topic><topic>Remission</topic><topic>Signal transduction</topic><topic>Spatial distribution</topic><topic>Stem cells</topic><topic>Steroids</topic><topic>Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schneider, Natália</creatorcontrib><creatorcontrib>Gonçalves, Fabiany da Costa</creatorcontrib><creatorcontrib>Pinto, Fernanda Otesbelgue</creatorcontrib><creatorcontrib>Lopez, Patrícia Luciana da Costa</creatorcontrib><creatorcontrib>Araújo, Anelise Bergmann</creatorcontrib><creatorcontrib>Pfaffenseller, 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one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schneider, Natália</au><au>Gonçalves, Fabiany da Costa</au><au>Pinto, Fernanda Otesbelgue</au><au>Lopez, Patrícia Luciana da Costa</au><au>Araújo, Anelise Bergmann</au><au>Pfaffenseller, Bianca</au><au>Passos, Eduardo Pandolfi</au><au>Cirne-Lima, Elizabeth Obino</au><au>Meurer, Luíse</au><au>Lamers, Marcelo Lazzaron</au><au>Paz, Ana Helena</au><au>Genetos, Damian Christopher</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-10</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0120538</spage><epage>e0120538</epage><pages>e0120538-e0120538</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25756665</pmid><doi>10.1371/journal.pone.0120538</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2015-03, Vol.10 (3), p.e0120538-e0120538 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1661987364 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Actin Adhesion tests Azathioprine Azathioprine - pharmacology Bone marrow Care and treatment Cell adhesion & migration Cell migration Cell Movement - drug effects Cell Shape - drug effects Cell size Cell Survival Cells, Cultured Cytokines Cytology Cytoskeleton Cytoskeleton - metabolism Dexamethasone Dexamethasone - pharmacology Dosage and administration Drug Evaluation, Preclinical Drugs Elongation Embryology Fibers Focal adhesion kinase Focal Adhesion Kinase 1 - metabolism Gastroenterology Gastrointestinal diseases Glucocorticoids Hepatology Humans Immune response Immune system Immunomodulation Immunosuppressive agents Immunosuppressive Agents - pharmacology Inflammation Inflammatory bowel disease Inflammatory bowel diseases Inflammatory diseases Intestine Kinases Laboratories Mesenchymal stem cells Mesenchymal Stromal Cells - physiology Mesenchyme Morphology Morphometry Physiological aspects Polarity Properties (attributes) Regulators Remission Signal transduction Spatial distribution Stem cells Steroids Therapy |
title | Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T05%3A23%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dexamethasone%20and%20azathioprine%20promote%20cytoskeletal%20changes%20and%20affect%20mesenchymal%20stem%20cell%20migratory%20behavior&rft.jtitle=PloS%20one&rft.au=Schneider,%20Nat%C3%A1lia&rft.date=2015-03-10&rft.volume=10&rft.issue=3&rft.spage=e0120538&rft.epage=e0120538&rft.pages=e0120538-e0120538&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0120538&rft_dat=%3Cgale_plos_%3EA426586827%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1661987364&rft_id=info:pmid/25756665&rft_galeid=A426586827&rft_doaj_id=oai_doaj_org_article_1cc599f80bef4e688de8b5ef9b9fb267&rfr_iscdi=true |