Mesenchymal stromal cells and polymeric vectors for tissue engineering of the central nervous system
Identifieur interne : 000713 ( Hal/Corpus ); précédent : 000712; suivant : 000714Mesenchymal stromal cells and polymeric vectors for tissue engineering of the central nervous system
Auteurs : Gaëtan DelcroixSource :
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Abstract
Mesenchymal stromal cells (MSCs) have several advantages for brain cell therapy. We first demonstrated that MSCs do not migrate in healthy rat brains whereas they were attracted by a lesion located far from their implantation site. However, we also confirmed that the poor cell survival and neuronal differentiation are the major obstacles encountered for brain cell therapy. Thus, we then focused on enhancing the neuronal differentiation potential of MSCs before transplantation, using an epidermal growth factor-basic fibroblast growth factor (EGF-bFGF) pre-treatment in vitro. Finally, we associated MSCs to polymeric vectors, the pharmacologically active microcarriers (PAMs), to increase cell survival and neuronal differentiation, and thereby favouring MSC tissue regeneration potential after transplantation. These PLGA microspheres were coated with a biomimetic surface of laminin, after demonstrating the benefits of this molecule on the neuronal differentiation potential of MSCs in vitro. After attachment of MSCs on their surface, neurotrophin releasing, laminin-coated PAMs have been evaluated in a rat model of Parkinson's disease. A significant functional recovery was observed compared to cells grafted without PAMs. This strategy is the first to give the proof of concept for the use of adult stem cells combined to bioactive polymeric vectors to protect the central nervous system in the context of Parkinson's disease.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mesenchymal stromal cells and polymeric vectors for tissue engineering of the central nervous system</title><title xml:lang="fr">Cellules stromales mésenchymateuses et vecteurs polymériques pour l'ingénierie tissulaire du système nerveux central</title><author><name sortKey="Delcroix, Gaetan" sort="Delcroix, Gaetan" uniqKey="Delcroix G" first="Gaëtan" last="Delcroix">Gaëtan Delcroix</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-3004" status="OLD"><orgName>Ingénierie de la vectorisation particulaire</orgName><desc><address><addrLine>Batiment IBT 10, Rue Andre Boquel 49100 Angers</addrLine><country key="FR"></country></address><ref type="url">http://www.u646.angers.inserm.fr/</ref></desc><listRelation><relation active="#struct-74911" type="direct"></relation><relation name="U646" active="#struct-303623" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-74911" type="direct"><org type="institution" xml:id="struct-74911" status="VALID"><orgName>Université d'Angers</orgName><orgName type="acronym">UA</orgName><desc><address><addrLine>40 rue de Rennes - BP 73532 - 49035 Angers cedex 01</addrLine><country key="FR"></country></address><ref type="url">http://www.univ-angers.fr/</ref></desc></org></tutelle><tutelle name="U646" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:tel-00476792</idno><idno type="halId">tel-00476792</idno><idno type="halUri">https://tel.archives-ouvertes.fr/tel-00476792</idno><idno type="url">https://tel.archives-ouvertes.fr/tel-00476792</idno><date when="2009-11-26">2009-11-26</date><idno type="wicri:Area/Hal/Corpus">000713</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Mesenchymal stromal cells and polymeric vectors for tissue engineering of the central nervous system</title><title xml:lang="fr">Cellules stromales mésenchymateuses et vecteurs polymériques pour l'ingénierie tissulaire du système nerveux central</title><author><name sortKey="Delcroix, Gaetan" sort="Delcroix, Gaetan" uniqKey="Delcroix G" first="Gaëtan" last="Delcroix">Gaëtan Delcroix</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-3004" status="OLD"><orgName>Ingénierie de la vectorisation particulaire</orgName><desc><address><addrLine>Batiment IBT 10, Rue Andre Boquel 49100 Angers</addrLine><country key="FR"></country></address><ref type="url">http://www.u646.angers.inserm.fr/</ref></desc><listRelation><relation active="#struct-74911" type="direct"></relation><relation name="U646" active="#struct-303623" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-74911" type="direct"><org type="institution" xml:id="struct-74911" status="VALID"><orgName>Université d'Angers</orgName><orgName type="acronym">UA</orgName><desc><address><addrLine>40 rue de Rennes - BP 73532 - 49035 Angers cedex 01</addrLine><country key="FR"></country></address><ref type="url">http://www.univ-angers.fr/</ref></desc></org></tutelle><tutelle name="U646" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author></analytic></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Mesenchymal stromal cells</term><term>Parkinson's disease</term><term>pharmacologically active microcarriers</term><term>tissue engineering</term></keywords><keywords scheme="mix" xml:lang="fr"><term>EGF-bFGF</term><term>Ingénierie tissulaire</term><term>cellules stromales mésenchymateuses</term><term>maladie de Parkinson</term><term>microcarriers</term><term>pharmacologiquement actifs</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mesenchymal stromal cells (MSCs) have several advantages for brain cell therapy. We first demonstrated that MSCs do not migrate in healthy rat brains whereas they were attracted by a lesion located far from their implantation site. However, we also confirmed that the poor cell survival and neuronal differentiation are the major obstacles encountered for brain cell therapy. Thus, we then focused on enhancing the neuronal differentiation potential of MSCs before transplantation, using an epidermal growth factor-basic fibroblast growth factor (EGF-bFGF) pre-treatment in vitro. Finally, we associated MSCs to polymeric vectors, the pharmacologically active microcarriers (PAMs), to increase cell survival and neuronal differentiation, and thereby favouring MSC tissue regeneration potential after transplantation. These PLGA microspheres were coated with a biomimetic surface of laminin, after demonstrating the benefits of this molecule on the neuronal differentiation potential of MSCs in vitro. After attachment of MSCs on their surface, neurotrophin releasing, laminin-coated PAMs have been evaluated in a rat model of Parkinson's disease. A significant functional recovery was observed compared to cells grafted without PAMs. This strategy is the first to give the proof of concept for the use of adult stem cells combined to bioactive polymeric vectors to protect the central nervous system in the context of Parkinson's disease.</div></front></TEI><hal api="V3"><titleStmt><title xml:lang="en">Mesenchymal stromal cells and polymeric vectors for tissue engineering of the central nervous system</title><title xml:lang="fr">Cellules stromales mésenchymateuses et vecteurs polymériques pour l'ingénierie tissulaire du système nerveux central</title><author role="aut"><persName><forename type="first">Gaëtan</forename><forename type="middle">J.-R.</forename><surname>Delcroix</surname></persName><email type="md5">05a06806f047b0f7d9dab550412a1827</email><email type="domain">gmail.com</email><idno type="halauthorid">482159</idno><affiliation ref="#struct-3004"></affiliation></author><editor role="depositor"><persName><forename>Anne-Marie</forename><surname>Plé</surname></persName><email type="md5">5ca69c6fb778f937942643081ad41dee</email><email type="domain">univ-angers.fr</email></editor></titleStmt><editionStmt><edition n="v1" type="current"><date type="whenSubmitted">2010-04-27 11:39:23</date><date type="whenModified">2010-04-27 12:53:43</date><date type="whenReleased">2010-04-27 12:53:43</date><date type="whenProduced">2009-11-26</date><date type="whenEndEmbargoed">2010-04-27</date><ref type="file" target="https://tel.archives-ouvertes.fr/tel-00476792/document"><date notBefore="2010-04-27"></date></ref><ref type="file" n="1" target="https://tel.archives-ouvertes.fr/tel-00476792/file/these_delcroix.pdf"><date notBefore="2010-04-27"></date></ref></edition><respStmt><resp>contributor</resp><name key="129499"><persName><forename>Anne-Marie</forename><surname>Plé</surname></persName><email type="md5">5ca69c6fb778f937942643081ad41dee</email><email type="domain">univ-angers.fr</email></name></respStmt></editionStmt><publicationStmt><distributor>CCSD</distributor><idno type="halId">tel-00476792</idno><idno type="halUri">https://tel.archives-ouvertes.fr/tel-00476792</idno><idno type="halBibtex">delcroix:tel-00476792</idno><idno type="halRefHtml">Biologie cellulaire. Université d'Angers, 2009. Français</idno><idno type="halRef">Biologie cellulaire. Université d'Angers, 2009. Français</idno></publicationStmt><seriesStmt><idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno><idno type="stamp" n="UNIV-ANGERS">Université d'Angers</idno><idno type="stamp" n="UNIV-ANGERS-THESE" p="UNIV-ANGERS">Thèses de l'Université d'Angers</idno></seriesStmt><notesStmt></notesStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Mesenchymal stromal cells and polymeric vectors for tissue engineering of the central nervous system</title><title xml:lang="fr">Cellules stromales mésenchymateuses et vecteurs polymériques pour l'ingénierie tissulaire du système nerveux central</title><author role="aut"><persName><forename type="first">Gaëtan</forename><forename type="middle">J.-R.</forename><surname>Delcroix</surname></persName><email type="md5">05a06806f047b0f7d9dab550412a1827</email><email type="domain">gmail.com</email><idno type="halauthorid">482159</idno><affiliation ref="#struct-3004"></affiliation></author></analytic><monogr><imprint><date type="dateDefended">2009-11-26</date></imprint><authority type="institution">Université d'Angers</authority><authority type="school">Ecole doctorale Biologie Santé</authority><authority type="supervisor">Claudia Montero-Menei</authority><authority type="jury">Joëlle Amédée ( Rapporteur )</authority><authority type="jury">Maria Blanco-Prieto ( Rapporteur )</authority><authority type="jury">Jean-Pierre Benoit ( Examinateur )</authority><authority type="jury">Phillipe Naveilhan ( Examinateur )</authority><authority type="jury">Luc Sensébé ( Examinateur )</authority><authority type="jury">Claudia Montero-Menei ( Directrice de thèse et Examinateur )</authority></monogr></biblStruct></sourceDesc><profileDesc><langUsage><language ident="fr">French</language></langUsage><textClass><keywords scheme="author"><term xml:lang="en">Parkinson's disease</term><term xml:lang="en">pharmacologically active microcarriers</term><term xml:lang="en">Mesenchymal stromal cells</term><term xml:lang="en">tissue engineering</term><term xml:lang="fr">Ingénierie tissulaire</term><term xml:lang="fr">cellules stromales mésenchymateuses</term><term xml:lang="fr">EGF-bFGF</term><term xml:lang="fr">maladie de Parkinson</term><term xml:lang="fr">microcarriers</term><term xml:lang="fr">pharmacologiquement actifs</term></keywords><classCode scheme="halDomain" n="sdv.bc">Life Sciences [q-bio]/Cellular Biology</classCode><classCode scheme="halDomain" n="sdv.neu">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]</classCode><classCode scheme="halTypology" n="THESE">Theses</classCode></textClass><abstract xml:lang="en">Mesenchymal stromal cells (MSCs) have several advantages for brain cell therapy. We first demonstrated that MSCs do not migrate in healthy rat brains whereas they were attracted by a lesion located far from their implantation site. However, we also confirmed that the poor cell survival and neuronal differentiation are the major obstacles encountered for brain cell therapy. Thus, we then focused on enhancing the neuronal differentiation potential of MSCs before transplantation, using an epidermal growth factor-basic fibroblast growth factor (EGF-bFGF) pre-treatment in vitro. Finally, we associated MSCs to polymeric vectors, the pharmacologically active microcarriers (PAMs), to increase cell survival and neuronal differentiation, and thereby favouring MSC tissue regeneration potential after transplantation. These PLGA microspheres were coated with a biomimetic surface of laminin, after demonstrating the benefits of this molecule on the neuronal differentiation potential of MSCs in vitro. After attachment of MSCs on their surface, neurotrophin releasing, laminin-coated PAMs have been evaluated in a rat model of Parkinson's disease. A significant functional recovery was observed compared to cells grafted without PAMs. This strategy is the first to give the proof of concept for the use of adult stem cells combined to bioactive polymeric vectors to protect the central nervous system in the context of Parkinson's disease.</abstract><abstract xml:lang="fr">Les cellules stromales mésenchymateuses (CSM) possèdent de nombreux atouts pour la thérapie cellulaire du cerveau. Nous avons tout d'abord démontré que les CSM ne migraient pas dans le cerveau de rats sains alors qu'elles étaient attirées par une lésion située à grande distance de leur site d'implantation. Nous avons également confirmé que la faible survie et différenciation neuronale des cellules in vivo constituent les obstacles majeurs à la thérapie cellulaire du cerveau. Par conséquent, nous nous sommes ensuite attachés à améliorer le potentiel de différenciation neuronal des CSM avant transplantation, à l'aide d'un pré-traitement en « epidermal growth factor » (EGF) et « basic fibroblast growth factor » (bFGF) in vitro. Finalement, nous avons associé des CSM à des vecteurs polymériques, les microcarriers pharmacologiquement actifs (MPA), afin de favoriser la survie, la différenciation neuronale et les capacités de réparation tissulaire des cellules après transplantation. Ces microsphères de PLGA ont ainsi été enrobées d'une surface biomimétique de laminine, après en avoir démontré les bénéfices sur la différenciation neuronale des CSM in vitro. Des CSM ont ensuite été mises en contact avec des MPA enrobées de laminine et libérant une neurotrophine, avant transplantation dans un modèle animal de la maladie de Parkinson. D'importants effets fonctionnels ont été observés par rapport à la greffe de cellules seules, et cette stratégie est la première à démontrer l'intérêt de cellules souches adultes associées à des vecteurs polymériques bioactifs pour protéger le système nerveux central dans le contexte de la maladie de Parkinson.</abstract></profileDesc></hal></record>Pour manipuler ce document sous Unix (Dilib)
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