Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease
Identifieur interne : 000A71 ( Hal/Corpus ); précédent : 000A70; suivant : 000A72Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease
Auteurs : Nicolas Daviaud ; Elisa Garbayo ; Laurence Sindji ; Alberto Martínez-Serrano ; Paul Schiller ; Claudia Montero-MeneiSource :
- Stem Cells Translational Medicine [ 2157-6580 ] ; 2015.
English descriptors
- mix :
Abstract
UNLABELLED: : Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD.
SIGNIFICANCE: Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms of marrow-isolated adult multilineage inducible cells and human neural stem cells both adhered to neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo organotypic model of PD made from brain sagittal slices.
Url:
DOI: 10.5966/sctm.2014-0139
Links to Exploration step
Hal:hal-01392449Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease</title>
<author><name sortKey="Daviaud, Nicolas" sort="Daviaud, Nicolas" uniqKey="Daviaud N" first="Nicolas" last="Daviaud">Nicolas Daviaud</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-180123" status="VALID"><orgName>Micro et nanomédecines biomimétiques</orgName>
<orgName type="acronym">MINT</orgName>
<desc><address><addrLine>Université d'Angers, 10 rue André Boquel 49100 Angers</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation><relation name="U1066" active="#struct-303623" type="direct"></relation>
<relation active="#struct-74911" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="U1066" 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>
<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>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Garbayo, Elisa" sort="Garbayo, Elisa" uniqKey="Garbayo E" first="Elisa" last="Garbayo">Elisa Garbayo</name>
</author>
<author><name sortKey="Sindji, Laurence" sort="Sindji, Laurence" uniqKey="Sindji L" first="Laurence" last="Sindji">Laurence Sindji</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-180123" status="VALID"><orgName>Micro et nanomédecines biomimétiques</orgName>
<orgName type="acronym">MINT</orgName>
<desc><address><addrLine>Université d'Angers, 10 rue André Boquel 49100 Angers</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation><relation name="U1066" active="#struct-303623" type="direct"></relation>
<relation active="#struct-74911" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="U1066" 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>
<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>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Martinez Serrano, Alberto" sort="Martinez Serrano, Alberto" uniqKey="Martinez Serrano A" first="Alberto" last="Martínez-Serrano">Alberto Martínez-Serrano</name>
</author>
<author><name sortKey="Schiller, Paul" sort="Schiller, Paul" uniqKey="Schiller P" first="Paul" last="Schiller">Paul Schiller</name>
</author>
<author><name sortKey="Montero Menei, Claudia" sort="Montero Menei, Claudia" uniqKey="Montero Menei C" first="Claudia" last="Montero-Menei">Claudia Montero-Menei</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-180123" status="VALID"><orgName>Micro et nanomédecines biomimétiques</orgName>
<orgName type="acronym">MINT</orgName>
<desc><address><addrLine>Université d'Angers, 10 rue André Boquel 49100 Angers</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation><relation name="U1066" active="#struct-303623" type="direct"></relation>
<relation active="#struct-74911" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="U1066" 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>
<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>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:hal-01392449</idno>
<idno type="halId">hal-01392449</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-01392449</idno>
<idno type="url">https://hal.archives-ouvertes.fr/hal-01392449</idno>
<idno type="doi">10.5966/sctm.2014-0139</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Hal/Corpus">000A71</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease</title>
<author><name sortKey="Daviaud, Nicolas" sort="Daviaud, Nicolas" uniqKey="Daviaud N" first="Nicolas" last="Daviaud">Nicolas Daviaud</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-180123" status="VALID"><orgName>Micro et nanomédecines biomimétiques</orgName>
<orgName type="acronym">MINT</orgName>
<desc><address><addrLine>Université d'Angers, 10 rue André Boquel 49100 Angers</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation><relation name="U1066" active="#struct-303623" type="direct"></relation>
<relation active="#struct-74911" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="U1066" 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>
<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>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Garbayo, Elisa" sort="Garbayo, Elisa" uniqKey="Garbayo E" first="Elisa" last="Garbayo">Elisa Garbayo</name>
</author>
<author><name sortKey="Sindji, Laurence" sort="Sindji, Laurence" uniqKey="Sindji L" first="Laurence" last="Sindji">Laurence Sindji</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-180123" status="VALID"><orgName>Micro et nanomédecines biomimétiques</orgName>
<orgName type="acronym">MINT</orgName>
<desc><address><addrLine>Université d'Angers, 10 rue André Boquel 49100 Angers</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation><relation name="U1066" active="#struct-303623" type="direct"></relation>
<relation active="#struct-74911" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="U1066" 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>
<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>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Martinez Serrano, Alberto" sort="Martinez Serrano, Alberto" uniqKey="Martinez Serrano A" first="Alberto" last="Martínez-Serrano">Alberto Martínez-Serrano</name>
</author>
<author><name sortKey="Schiller, Paul" sort="Schiller, Paul" uniqKey="Schiller P" first="Paul" last="Schiller">Paul Schiller</name>
</author>
<author><name sortKey="Montero Menei, Claudia" sort="Montero Menei, Claudia" uniqKey="Montero Menei C" first="Claudia" last="Montero-Menei">Claudia Montero-Menei</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-180123" status="VALID"><orgName>Micro et nanomédecines biomimétiques</orgName>
<orgName type="acronym">MINT</orgName>
<desc><address><addrLine>Université d'Angers, 10 rue André Boquel 49100 Angers</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation><relation name="U1066" active="#struct-303623" type="direct"></relation>
<relation active="#struct-74911" type="direct"></relation>
</listRelation>
<tutelles><tutelle name="U1066" 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>
<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>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.5966/sctm.2014-0139</idno>
<series><title level="j">Stem Cells Translational Medicine</title>
<idno type="ISSN">2157-6580</idno>
<imprint><date type="datePub">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Laminin</term>
<term>Mesenchymal Stem Cells</term>
<term>Neural stem cells</term>
<term>Neurotrophin-3</term>
<term>Organotypic slice culture</term>
<term>Stanniocalcin-1</term>
<term>tissue engineering</term>
<term>vascular endothelial growth factor</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">UNLABELLED: : Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD.
SIGNIFICANCE: Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms of marrow-isolated adult multilineage inducible cells and human neural stem cells both adhered to neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo organotypic model of PD made from brain sagittal slices.
</div>
</front>
</TEI>
<hal api="V3"><titleStmt><title xml:lang="en">Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease</title>
<author role="aut"><persName><forename type="first">Nicolas</forename>
<surname>Daviaud</surname>
</persName>
<idno type="halauthorid">1410747</idno>
<affiliation ref="#struct-180123"></affiliation>
</author>
<author role="aut"><persName><forename type="first">Elisa</forename>
<surname>Garbayo</surname>
</persName>
<idno type="halauthorid">553156</idno>
</author>
<author role="aut"><persName><forename type="first">Laurence</forename>
<surname>Sindji</surname>
</persName>
<email type="md5">52862afdd61ada20b2a39dfd18fe1037</email>
<email type="domain">univ-angers.fr</email>
<idno type="halauthorid">1311458</idno>
<affiliation ref="#struct-180123"></affiliation>
</author>
<author role="aut"><persName><forename type="first">Alberto</forename>
<surname>Martínez-Serrano</surname>
</persName>
<idno type="halauthorid">1410748</idno>
</author>
<author role="aut"><persName><forename type="first">Paul</forename>
<surname>Schiller</surname>
</persName>
<idno type="halauthorid">1410749</idno>
</author>
<author role="aut"><persName><forename type="first">Claudia</forename>
<surname>Montero-Menei</surname>
</persName>
<email type="md5">d97343aa05448b56713ddd72c2312bea</email>
<email type="domain">univ-angers.fr</email>
<idno type="halauthorid">1311463</idno>
<affiliation ref="#struct-180123"></affiliation>
</author>
<editor role="depositor"><persName><forename>Okina</forename>
<surname>Université d'Angers</surname>
</persName>
<email type="md5">b5db9c104e451c4c3e7e86bba508166f</email>
<email type="domain">contact.univ-angers.fr</email>
</editor>
</titleStmt>
<editionStmt><edition n="v1" type="current"><date type="whenSubmitted">2016-11-04 13:48:47</date>
<date type="whenModified">2016-11-05 01:00:40</date>
<date type="whenReleased">2016-11-04 13:48:47</date>
<date type="whenProduced">2015</date>
</edition>
<respStmt><resp>contributor</resp>
<name key="300611"><persName><forename>Okina</forename>
<surname>Université d'Angers</surname>
</persName>
<email type="md5">b5db9c104e451c4c3e7e86bba508166f</email>
<email type="domain">contact.univ-angers.fr</email>
</name>
</respStmt>
</editionStmt>
<publicationStmt><distributor>CCSD</distributor>
<idno type="halId">hal-01392449</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-01392449</idno>
<idno type="halBibtex">daviaud:hal-01392449</idno>
<idno type="halRefHtml">Stem Cells Translational Medicine, 2015, 4 (7), pp.670-684. <10.5966/sctm.2014-0139></idno>
<idno type="halRef">Stem Cells Translational Medicine, 2015, 4 (7), pp.670-684. <10.5966/sctm.2014-0139></idno>
</publicationStmt>
<seriesStmt><idno type="stamp" n="UNIV-ANGERS">Université d'Angers</idno>
</seriesStmt>
<notesStmt><note type="audience" n="2">International</note>
<note type="popular" n="0">No</note>
<note type="peer" n="1">Yes</note>
</notesStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease</title>
<author role="aut"><persName><forename type="first">Nicolas</forename>
<surname>Daviaud</surname>
</persName>
<idno type="halauthorid">1410747</idno>
<affiliation ref="#struct-180123"></affiliation>
</author>
<author role="aut"><persName><forename type="first">Elisa</forename>
<surname>Garbayo</surname>
</persName>
<idno type="halauthorid">553156</idno>
</author>
<author role="aut"><persName><forename type="first">Laurence</forename>
<surname>Sindji</surname>
</persName>
<email type="md5">52862afdd61ada20b2a39dfd18fe1037</email>
<email type="domain">univ-angers.fr</email>
<idno type="halauthorid">1311458</idno>
<affiliation ref="#struct-180123"></affiliation>
</author>
<author role="aut"><persName><forename type="first">Alberto</forename>
<surname>Martínez-Serrano</surname>
</persName>
<idno type="halauthorid">1410748</idno>
</author>
<author role="aut"><persName><forename type="first">Paul</forename>
<surname>Schiller</surname>
</persName>
<idno type="halauthorid">1410749</idno>
</author>
<author role="aut"><persName><forename type="first">Claudia</forename>
<surname>Montero-Menei</surname>
</persName>
<email type="md5">d97343aa05448b56713ddd72c2312bea</email>
<email type="domain">univ-angers.fr</email>
<idno type="halauthorid">1311463</idno>
<affiliation ref="#struct-180123"></affiliation>
</author>
</analytic>
<monogr><idno type="halJournalId" status="INCOMING">111686</idno>
<idno type="issn">2157-6580</idno>
<title level="j">Stem Cells Translational Medicine</title>
<imprint><biblScope unit="volume">4</biblScope>
<biblScope unit="issue">7</biblScope>
<biblScope unit="pp">670-684</biblScope>
<date type="datePub">2015</date>
</imprint>
</monogr>
<idno type="doi">10.5966/sctm.2014-0139</idno>
<idno type="okina">ua13173</idno>
</biblStruct>
</sourceDesc>
<profileDesc><langUsage><language ident="en">English</language>
</langUsage>
<textClass><keywords scheme="author"><term xml:lang="en">Laminin</term>
<term xml:lang="en">Mesenchymal Stem Cells</term>
<term xml:lang="en">Neural stem cells</term>
<term xml:lang="en">Neurotrophin-3</term>
<term xml:lang="en">Organotypic slice culture</term>
<term xml:lang="en">Stanniocalcin-1</term>
<term xml:lang="en">tissue engineering</term>
<term xml:lang="en">vascular endothelial growth factor</term>
</keywords>
<classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode>
<classCode scheme="halTypology" n="ART">Journal articles</classCode>
</textClass>
<abstract xml:lang="en">UNLABELLED: : Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD.
SIGNIFICANCE: Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms of marrow-isolated adult multilineage inducible cells and human neural stem cells both adhered to neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo organotypic model of PD made from brain sagittal slices.
</abstract>
</profileDesc>
</hal>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Hal/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A71 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Hal/Corpus/biblio.hfd -nk 000A71 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= Hal |étape= Corpus |type= RBID |clé= Hal:hal-01392449 |texte= Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease }}
![]() | This area was generated with Dilib version V0.6.29. | ![]() |