Journal article Open Access
Le Blon, Debbie; Guglielmetti, Caroline; Hoornaert, Chloé; Quarta, Alessandra; Daans, Jasmijn; Dooley, Dearbhaile; Lemmens, Evi; Praet, Jelle; De Vocht, Nathalie; Reekmans, Kristien; Santermans, Eva; Hens, Niel; Goossens, Herman; Verhoye, Marleen; Van der Linden, Annemie; Berneman, Zwi; Hendrix, Sven; Ponsaerts, Peter
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<foaf:Organization> <foaf:name>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Hoornaert, Chloé</foaf:name> <foaf:givenName>Chloé</foaf:givenName> <foaf:familyName>Hoornaert</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Quarta, Alessandra</foaf:name> <foaf:givenName>Alessandra</foaf:givenName> <foaf:familyName>Quarta</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Daans, Jasmijn</foaf:name> <foaf:givenName>Jasmijn</foaf:givenName> <foaf:familyName>Daans</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Dooley, Dearbhaile</foaf:name> <foaf:givenName>Dearbhaile</foaf:givenName> <foaf:familyName>Dooley</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Lemmens, Evi</foaf:name> <foaf:givenName>Evi</foaf:givenName> <foaf:familyName>Lemmens</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Praet, Jelle</foaf:name> <foaf:givenName>Jelle</foaf:givenName> <foaf:familyName>Praet</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>De Vocht, Nathalie</foaf:name> <foaf:givenName>Nathalie</foaf:givenName> <foaf:familyName>De Vocht</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Reekmans, Kristien</foaf:name> <foaf:givenName>Kristien</foaf:givenName> <foaf:familyName>Reekmans</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Santermans, Eva</foaf:name> <foaf:givenName>Eva</foaf:givenName> <foaf:familyName>Santermans</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Center for Statistics, I-Biostat, Hasselt University, Agoralaan building D, 3590, Diepenbeek, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Hens, Niel</foaf:name> <foaf:givenName>Niel</foaf:givenName> <foaf:familyName>Hens</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Center for Statistics, I-Biostat, Hasselt University, Agoralaan building D, 3590, Diepenbeek, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Goossens, Herman</foaf:name> <foaf:givenName>Herman</foaf:givenName> <foaf:familyName>Goossens</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Verhoye, Marleen</foaf:name> <foaf:givenName>Marleen</foaf:givenName> <foaf:familyName>Verhoye</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Van der Linden, Annemie</foaf:name> <foaf:givenName>Annemie</foaf:givenName> <foaf:familyName>Van der Linden</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Berneman, Zwi</foaf:name> <foaf:givenName>Zwi</foaf:givenName> <foaf:familyName>Berneman</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Hendrix, Sven</foaf:name> <foaf:givenName>Sven</foaf:givenName> <foaf:familyName>Hendrix</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:creator> <rdf:Description> <rdf:type rdf:resource="http://xmlns.com/foaf/0.1/Agent"/> <foaf:name>Ponsaerts, Peter</foaf:name> <foaf:givenName>Peter</foaf:givenName> <foaf:familyName>Ponsaerts</foaf:familyName> <org:memberOf> <foaf:Organization> <foaf:name>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</foaf:name> </foaf:Organization> </org:memberOf> </rdf:Description> </dct:creator> <dct:title>Intracerebral transplantation of interleukin 13-producing mesenchymal stem cells limits microgliosis, oligodendrocyte loss and demyelination in the cuprizone mouse model</dct:title> <dct:publisher> <foaf:Agent> <foaf:name>Zenodo</foaf:name> </foaf:Agent> </dct:publisher> <dct:issued rdf:datatype="http://www.w3.org/2001/XMLSchema#gYear">2016</dct:issued> <dcat:keyword>Interleukin 13</dcat:keyword> <dcat:keyword>Mesenchymal stem cells</dcat:keyword> <dcat:keyword>Neuroinflammation</dcat:keyword> <dcat:keyword>Transplantation</dcat:keyword> <dcat:keyword>Magnetic resonance imaging</dcat:keyword> <frapo:isFundedBy rdf:resource="info:eu-repo/grantAgreement/EC/FP7/278850/"/> <schema:funder> <foaf:Organization> <dct:identifier rdf:datatype="http://www.w3.org/2001/XMLSchema#string">10.13039/501100000780</dct:identifier> <foaf:name>European Commission</foaf:name> </foaf:Organization> </schema:funder> <dct:issued rdf:datatype="http://www.w3.org/2001/XMLSchema#date">2016-11-09</dct:issued> <owl:sameAs rdf:resource="https://zenodo.org/record/166404"/> <adms:identifier> <adms:Identifier> <skos:notation rdf:datatype="http://www.w3.org/2001/XMLSchema#anyURI">https://zenodo.org/record/166404</skos:notation> <adms:schemeAgency>url</adms:schemeAgency> </adms:Identifier> </adms:identifier> <owl:sameAs rdf:resource="https://doi.org/10.1186/s12974-016-0756-7"/> <dct:isPartOf rdf:resource="https://zenodo.org/communities/ecfunded"/> <dct:isPartOf rdf:resource="https://zenodo.org/communities/fp7-bmc"/> <dct:description><p><strong>Background: </strong>Promoting the neuroprotective and repair-inducing effector functions of microglia and macrophages, by means of M2 polarisation or alternative activation, is expected to become a new therapeutic approach for central nervous system (CNS) disorders in which detrimental pro-inflammatory microglia and/or macrophages display a major contribution to the neuropathology. In this study, we present a novel in vivo approach using intracerebral grafting of mesenchymal stem cells (MSC) genetically engineered to secrete interleukin 13 (IL13-MSC).</p><p><strong>Methods: </strong>In the first experimental setup, control MSC and IL13-MSC were grafted in the CNS of eGFP<sup>+</sup> bone marrow chimaeric C57BL/6 mice to histologically evaluate IL13-mediated expression of several markers associated with alternative activation, including arginase1 and Ym1, on MSC graft-recognising microglia and MSC graft-infiltrating macrophages. In the second experimental setup, IL13-MSC were grafted on the right side (or on both the right and left sides) of the <i>splenium</i> of the <i>corpus callosum</i> in wild-type C57BL/6 mice and in C57BL/6 CX<sub>3</sub>CR1<sup>eGFP/+</sup>CCR2<sup>RFP/+</sup> transgenic mice. Next, CNS inflammation and demyelination was induced by means of a cuprizone-supplemented diet. The influence of IL13-MSC grafting on neuropathological alterations was monitored by non-invasive <i>T</i> <sub>2</sub>-weighted magnetic resonance imaging (MRI) and quantitative histological analyses, as compared to cuprizone-treated mice with control MSC grafts and/or cuprizone-treated mice without MSC injection.</p><p><strong>Results: </strong>In the first part of this study, we demonstrate that MSC graft-associated microglia and MSC graft-infiltrating macrophages are forced into alternative activation upon grafting of IL13-MSC, but not upon grafting of control MSC. In the second part of this study, we demonstrate that grafting of IL13-MSC, in addition to the recruitment of M2 polarised macrophages, limits cuprizone-induced microgliosis, oligodendrocyte death and demyelination. Furthermore, we here demonstrate that injection of IL13-MSC at both sides of the splenium leads to a superior protective effect as compared to a single injection at one side of the splenium.</p><p><strong>Conclusions: </strong>Controlled and localised production of IL13 by means of intracerebral MSC grafting has the potential to modulate cell graft- and pathology-associated microglial/macrophage responses, and to interfere with oligodendrocyte death and demyelinating events in the cuprizone mouse model.</p></dct:description> <dct:accessRights rdf:resource="http://publications.europa.eu/resource/authority/access-right/PUBLIC"/> <dct:accessRights> <dct:RightsStatement rdf:about="info:eu-repo/semantics/openAccess"> <rdfs:label>Open Access</rdfs:label> </dct:RightsStatement> </dct:accessRights> <dcat:distribution> <dcat:Distribution> <dct:license rdf:resource="https://creativecommons.org/licenses/by/4.0/legalcode"/> <dcat:accessURL rdf:resource="https://zenodo.org/record/166404"/> </dcat:Distribution> </dcat:distribution> <dcat:distribution> <dcat:Distribution> <dcat:accessURL>https://doi.org/10.1186/s12974-016-0756-7</dcat:accessURL> <dcat:byteSize>3512817</dcat:byteSize> <dcat:downloadURL>https://zenodo.org/record/166404/files/12974_2016_Article_756.pdf</dcat:downloadURL> <dcat:mediaType>application/pdf</dcat:mediaType> </dcat:Distribution> </dcat:distribution> <dcat:distribution> <dcat:Distribution> <dcat:accessURL>https://doi.org/10.1186/s12974-016-0756-7</dcat:accessURL> <dcat:byteSize>32424</dcat:byteSize> <dcat:downloadURL>https://zenodo.org/record/166404/files/12974_2016_Article_756.xml.Meta</dcat:downloadURL> </dcat:Distribution> </dcat:distribution> </rdf:Description> <foaf:Project rdf:about="info:eu-repo/grantAgreement/EC/FP7/278850/"> <dct:identifier rdf:datatype="http://www.w3.org/2001/XMLSchema#string">278850</dct:identifier> <dct:title>Imaging of Neuroinflammation in Neurodegenerative Diseases</dct:title> <frapo:isAwardedBy> <foaf:Organization> <dct:identifier rdf:datatype="http://www.w3.org/2001/XMLSchema#string">10.13039/501100000780</dct:identifier> <foaf:name>European Commission</foaf:name> </foaf:Organization> </frapo:isAwardedBy> </foaf:Project> </rdf:RDF>
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