Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson's Disease.
Identifieur interne : 000075 ( Main/Exploration ); précédent : 000074; suivant : 000076Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson's Disease.
Auteurs : Fábio G. Teixeira [Portugal] ; Miguel M. Carvalho [Portugal] ; Krishna M. Panchalingam [Canada] ; Ana J. Rodrigues [Portugal] ; Bárbara Mendes-Pinheiro [Portugal] ; Sandra Anjo [Portugal] ; Bruno Manadas [Portugal] ; Leo A. Behie [Canada] ; Nuno Sousa [Portugal] ; Ant Nio J. Salgado [Portugal]Source :
- Stem cells translational medicine [ 2157-6564 ] ; 2017.
Abstract
Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i.e., conditioned medium). In this study, we have characterized the MSC secretome by proteomic-based analysis, investigating its therapeutic effects on the physiological recovery of a 6-hydroxidopamine (6-OHDA) PD rat model. For this purpose, we injected MSC secretome into the substantia nigra (SNc) and striatum (STR), characterizing the behavioral performance and determining histological parameters for injected animals versus untreated groups. We observed that the secretome potentiated the increase of dopaminergic neurons (i.e., tyrosine hydroxylase-positive cells) and neuronal terminals in the SNc and STR, respectively, thereby supporting the recovery observed in the Parkinsonian rats' motor performance outcomes (assessed by rotarod and staircase tests). Finally, proteomic characterization of the MSC secretome (through combined mass spectrometry analysis and Bioplex assays) revealed the presence of important neuroregulatory molecules, namely cystatin C, glia-derived nexin, galectin-1, pigment epithelium-derived factor, vascular endothelial growth factor, brain-derived neurotrophic factor, interleukin-6, and glial cell line-derived neurotrophic factor. Overall, we concluded that the use of human MSC secretome alone was able to partially revert the motor phenotype and the neuronal structure of 6-OHDA PD animals. This indicates that the human MSC secretome could represent a novel therapeutic for the treatment of PD. Stem Cells Translational Medicine 2017;6:634-646.
DOI: 10.5966/sctm.2016-0071
PubMed: 28191785
Affiliations:
- Canada, Portugal
- Alberta, Région Nord (Portugal)
- Braga, Calgary
- Université de Calgary, Université du Minho
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Teixeira</name><affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga</wicri:regionArea><orgName type="university">Université du Minho</orgName><placeName><settlement type="city">Braga</settlement><region>Région Nord (Portugal)</region></placeName></affiliation></author><author><name sortKey="Carvalho, Miguel M" sort="Carvalho, Miguel M" uniqKey="Carvalho M" first="Miguel M" last="Carvalho">Miguel M. Carvalho</name><affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga</wicri:regionArea><orgName type="university">Université du Minho</orgName><placeName><settlement type="city">Braga</settlement><region>Région Nord (Portugal)</region></placeName></affiliation></author><author><name sortKey="Panchalingam, Krishna M" sort="Panchalingam, Krishna M" uniqKey="Panchalingam K" first="Krishna M" last="Panchalingam">Krishna M. 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Rodrigues</name><affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga</wicri:regionArea><orgName type="university">Université du Minho</orgName><placeName><settlement type="city">Braga</settlement><region>Région Nord (Portugal)</region></placeName></affiliation></author><author><name sortKey="Mendes Pinheiro, Barbara" sort="Mendes Pinheiro, Barbara" uniqKey="Mendes Pinheiro B" first="Bárbara" last="Mendes-Pinheiro">Bárbara Mendes-Pinheiro</name><affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga</wicri:regionArea><orgName type="university">Université du Minho</orgName><placeName><settlement type="city">Braga</settlement><region>Région Nord (Portugal)</region></placeName></affiliation></author><author><name sortKey="Anjo, Sandra" sort="Anjo, Sandra" uniqKey="Anjo S" first="Sandra" last="Anjo">Sandra Anjo</name><affiliation wicri:level="1"><nlm:affiliation>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra</wicri:regionArea><wicri:noRegion>Coimbra</wicri:noRegion></affiliation></author><author><name sortKey="Manadas, Bruno" sort="Manadas, Bruno" uniqKey="Manadas B" first="Bruno" last="Manadas">Bruno Manadas</name><affiliation wicri:level="1"><nlm:affiliation>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra</wicri:regionArea><wicri:noRegion>Coimbra</wicri:noRegion></affiliation></author><author><name sortKey="Behie, Leo A" sort="Behie, Leo A" uniqKey="Behie L" first="Leo A" last="Behie">Leo A. Behie</name><affiliation wicri:level="4"><nlm:affiliation>Pharmaceutical Production Research Facility, Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, Alberta, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pharmaceutical Production Research Facility, Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, Alberta</wicri:regionArea><orgName type="university">Université de Calgary</orgName><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author><author><name sortKey="Sousa, Nuno" sort="Sousa, Nuno" uniqKey="Sousa N" first="Nuno" last="Sousa">Nuno Sousa</name><affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga</wicri:regionArea><orgName type="university">Université du Minho</orgName><placeName><settlement type="city">Braga</settlement><region>Région Nord (Portugal)</region></placeName></affiliation></author><author><name sortKey="Salgado, Ant Nio J" sort="Salgado, Ant Nio J" uniqKey="Salgado A" first="Ant Nio J" last="Salgado">Ant Nio J. Salgado</name><affiliation wicri:level="4"><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga</wicri:regionArea><orgName type="university">Université du Minho</orgName><placeName><settlement type="city">Braga</settlement><region>Région Nord (Portugal)</region></placeName></affiliation></author></analytic><series><title level="j">Stem cells translational medicine</title><idno type="ISSN">2157-6564</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i.e., conditioned medium). In this study, we have characterized the MSC secretome by proteomic-based analysis, investigating its therapeutic effects on the physiological recovery of a 6-hydroxidopamine (6-OHDA) PD rat model. For this purpose, we injected MSC secretome into the substantia nigra (SNc) and striatum (STR), characterizing the behavioral performance and determining histological parameters for injected animals versus untreated groups. We observed that the secretome potentiated the increase of dopaminergic neurons (i.e., tyrosine hydroxylase-positive cells) and neuronal terminals in the SNc and STR, respectively, thereby supporting the recovery observed in the Parkinsonian rats' motor performance outcomes (assessed by rotarod and staircase tests). Finally, proteomic characterization of the MSC secretome (through combined mass spectrometry analysis and Bioplex assays) revealed the presence of important neuroregulatory molecules, namely cystatin C, glia-derived nexin, galectin-1, pigment epithelium-derived factor, vascular endothelial growth factor, brain-derived neurotrophic factor, interleukin-6, and glial cell line-derived neurotrophic factor. Overall, we concluded that the use of human MSC secretome alone was able to partially revert the motor phenotype and the neuronal structure of 6-OHDA PD animals. This indicates that the human MSC secretome could represent a novel therapeutic for the treatment of PD. Stem Cells Translational Medicine 2017;6:634-646.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Portugal</li></country><region><li>Alberta</li><li>Région Nord (Portugal)</li></region><settlement><li>Braga</li><li>Calgary</li></settlement><orgName><li>Université de Calgary</li><li>Université du Minho</li></orgName></list><tree><country name="Portugal"><region name="Région Nord (Portugal)"><name sortKey="Teixeira, Fabio G" sort="Teixeira, Fabio G" uniqKey="Teixeira F" first="Fábio G" last="Teixeira">Fábio G. Teixeira</name></region><name sortKey="Anjo, Sandra" sort="Anjo, Sandra" uniqKey="Anjo S" first="Sandra" last="Anjo">Sandra Anjo</name><name sortKey="Carvalho, Miguel M" sort="Carvalho, Miguel M" uniqKey="Carvalho M" first="Miguel M" last="Carvalho">Miguel M. Carvalho</name><name sortKey="Manadas, Bruno" sort="Manadas, Bruno" uniqKey="Manadas B" first="Bruno" last="Manadas">Bruno Manadas</name><name sortKey="Mendes Pinheiro, Barbara" sort="Mendes Pinheiro, Barbara" uniqKey="Mendes Pinheiro B" first="Bárbara" last="Mendes-Pinheiro">Bárbara Mendes-Pinheiro</name><name sortKey="Rodrigues, Ana J" sort="Rodrigues, Ana J" uniqKey="Rodrigues A" first="Ana J" last="Rodrigues">Ana J. Rodrigues</name><name sortKey="Salgado, Ant Nio J" sort="Salgado, Ant Nio J" uniqKey="Salgado A" first="Ant Nio J" last="Salgado">Ant Nio J. Salgado</name><name sortKey="Sousa, Nuno" sort="Sousa, Nuno" uniqKey="Sousa N" first="Nuno" last="Sousa">Nuno Sousa</name></country><country name="Canada"><region name="Alberta"><name sortKey="Panchalingam, Krishna M" sort="Panchalingam, Krishna M" uniqKey="Panchalingam K" first="Krishna M" last="Panchalingam">Krishna M. Panchalingam</name></region><name sortKey="Behie, Leo A" sort="Behie, Leo A" uniqKey="Behie L" first="Leo A" last="Behie">Leo A. Behie</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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