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 : 000074 ( PubMed/Corpus ); précédent : 000073; suivant : 000075Impact 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 ; Miguel M. Carvalho ; Krishna M. Panchalingam ; Ana J. Rodrigues ; Bárbara Mendes-Pinheiro ; Sandra Anjo ; Bruno Manadas ; Leo A. Behie ; Nuno Sousa ; Ant Nio J. SalgadoSource :
- 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
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Teixeira</name><affiliation><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation></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><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation></affiliation></author><author><name sortKey="Panchalingam, Krishna M" sort="Panchalingam, Krishna M" uniqKey="Panchalingam K" first="Krishna M" last="Panchalingam">Krishna M. Panchalingam</name><affiliation><nlm:affiliation>Pharmaceutical Production Research Facility, Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, Alberta, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Rodrigues, Ana J" sort="Rodrigues, Ana J" uniqKey="Rodrigues A" first="Ana J" last="Rodrigues">Ana J. Rodrigues</name><affiliation><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation></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><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation></affiliation></author><author><name sortKey="Anjo, Sandra" sort="Anjo, Sandra" uniqKey="Anjo S" first="Sandra" last="Anjo">Sandra Anjo</name><affiliation><nlm:affiliation>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.</nlm:affiliation></affiliation></author><author><name sortKey="Manadas, Bruno" sort="Manadas, Bruno" uniqKey="Manadas B" first="Bruno" last="Manadas">Bruno Manadas</name><affiliation><nlm:affiliation>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.</nlm:affiliation></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><nlm:affiliation>Pharmaceutical Production Research Facility, Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, Alberta, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Sousa, Nuno" sort="Sousa, Nuno" uniqKey="Sousa N" first="Nuno" last="Sousa">Nuno Sousa</name><affiliation><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation></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><nlm:affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</nlm:affiliation></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><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">28191785</PMID><DateCreated><Year>2017</Year><Month>02</Month><Day>13</Day></DateCreated><DateRevised><Year>2017</Year><Month>02</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">2157-6564</ISSN><JournalIssue CitedMedium="Print"><Volume>6</Volume><Issue>2</Issue><PubDate><Year>2017</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Stem cells translational medicine</Title><ISOAbbreviation>Stem Cells Transl Med</ISOAbbreviation></Journal><ArticleTitle>Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson's Disease.</ArticleTitle><Pagination><MedlinePgn>634-646</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.5966/sctm.2016-0071</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Teixeira</LastName><ForeName>Fábio G</ForeName><Initials>FG</Initials><AffiliationInfo><Affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carvalho</LastName><ForeName>Miguel M</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Panchalingam</LastName><ForeName>Krishna M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Pharmaceutical Production Research Facility, Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, Alberta, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodrigues</LastName><ForeName>Ana J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mendes-Pinheiro</LastName><ForeName>Bárbara</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anjo</LastName><ForeName>Sandra</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Manadas</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biocant - Biotechnology Innovation Center, Cantanhede, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Behie</LastName><ForeName>Leo A</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>Pharmaceutical Production Research Facility, Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, Alberta, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sousa</LastName><ForeName>Nuno</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salgado</LastName><ForeName>António J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>09</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Stem Cells Transl Med</MedlineTA><NlmUniqueID>101578022</NlmUniqueID><ISSNLinking>2157-6564</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Dopaminergic neurons</Keyword><Keyword MajorTopicYN="N">Mesenchymal stem cells</Keyword><Keyword MajorTopicYN="N">Neuroprotection</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">Secretome</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>02</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>08</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>2</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>2</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>2</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28191785</ArticleId><ArticleId IdType="doi">10.5966/sctm.2016-0071</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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