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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A microfluidic-based neurotoxin concentration gradient for the generation of an <italic>in vitro</italic> model of Parkinson’s disease</title><author><name sortKey="Seidi, Azadeh" sort="Seidi, Azadeh" uniqKey="Seidi A" first="Azadeh" last="Seidi">Azadeh Seidi</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation></author><author><name sortKey="Kaji, Hirokazu" sort="Kaji, Hirokazu" uniqKey="Kaji H" first="Hirokazu" last="Kaji">Hirokazu Kaji</name><affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff></affiliation><affiliation><nlm:aff id="a3">Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan</nlm:aff></affiliation></author><author><name sortKey="Annabi, Nasim" sort="Annabi, Nasim" uniqKey="Annabi N" first="Nasim" last="Annabi">Nasim Annabi</name><affiliation><nlm:aff id="a4">School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, New South Wales 2006, Australia</nlm:aff></affiliation></author><author><name sortKey="Ostrovidov, Serge" sort="Ostrovidov, Serge" uniqKey="Ostrovidov S" first="Serge" last="Ostrovidov">Serge Ostrovidov</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation></author><author><name sortKey="Ramalingam, Murugan" sort="Ramalingam, Murugan" uniqKey="Ramalingam M" first="Murugan" last="Ramalingam">Murugan Ramalingam</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation><affiliation><nlm:aff id="a5">Faculte de Medecine, National Institute of Health and Medical Research U977, Université de Strasbourg, Strasbourg, Cedex 67085, France</nlm:aff></affiliation></author><author><name sortKey="Khademhosseini, Ali" sort="Khademhosseini, Ali" uniqKey="Khademhosseini A" first="Ali" last="Khademhosseini">Ali Khademhosseini</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation><affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff></affiliation><affiliation><nlm:aff id="a6">Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21799720</idno><idno type="pmc">3145239</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145239</idno><idno type="RBID">PMC:3145239</idno><idno type="doi">10.1063/1.3580756</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000679</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000679</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A microfluidic-based neurotoxin concentration gradient for the generation of an <italic>in vitro</italic> model of Parkinson’s disease</title><author><name sortKey="Seidi, Azadeh" sort="Seidi, Azadeh" uniqKey="Seidi A" first="Azadeh" last="Seidi">Azadeh Seidi</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation></author><author><name sortKey="Kaji, Hirokazu" sort="Kaji, Hirokazu" uniqKey="Kaji H" first="Hirokazu" last="Kaji">Hirokazu Kaji</name><affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff></affiliation><affiliation><nlm:aff id="a3">Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan</nlm:aff></affiliation></author><author><name sortKey="Annabi, Nasim" sort="Annabi, Nasim" uniqKey="Annabi N" first="Nasim" last="Annabi">Nasim Annabi</name><affiliation><nlm:aff id="a4">School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, New South Wales 2006, Australia</nlm:aff></affiliation></author><author><name sortKey="Ostrovidov, Serge" sort="Ostrovidov, Serge" uniqKey="Ostrovidov S" first="Serge" last="Ostrovidov">Serge Ostrovidov</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation></author><author><name sortKey="Ramalingam, Murugan" sort="Ramalingam, Murugan" uniqKey="Ramalingam M" first="Murugan" last="Ramalingam">Murugan Ramalingam</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation><affiliation><nlm:aff id="a5">Faculte de Medecine, National Institute of Health and Medical Research U977, Université de Strasbourg, Strasbourg, Cedex 67085, France</nlm:aff></affiliation></author><author><name sortKey="Khademhosseini, Ali" sort="Khademhosseini, Ali" uniqKey="Khademhosseini A" first="Ali" last="Khademhosseini">Ali Khademhosseini</name><affiliation><nlm:aff id="a1">WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</nlm:aff></affiliation><affiliation><nlm:aff id="a2">Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</nlm:aff></affiliation><affiliation><nlm:aff id="a6">Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Biomicrofluidics</title><idno type="ISSN">1932-1058</idno><idno type="eISSN">1932-1058</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In this study, we developed a miniaturized microfluidic-based high-throughput cell toxicity assay to create an <italic>in vitro</italic> model of Parkinson’s disease (PD). In particular, we generated concentration gradients of 6-hydroxydopamine (6-OHDA) to trigger a process of neuronal apoptosis in pheochromocytoma PC12 neuronal cell line. PC12 cells were cultured in a microfluidic channel, and a concentration gradient of 6-OHDA was generated in the channel by using a back and forth movement of the fluid flow. Cellular apoptosis was then analyzed along the channel. The results indicate that at low concentrations of 6-OHDA along the gradient (i.e., approximately less than 260 μM), the neuronal death in the channel was mainly induced by apoptosis, while at higher concentrations, 6-OHDA induced neuronal death mainly through necrosis. Thus, this concentration appears to be useful for creating an <italic>in vitro</italic> model of PD by inducing the highest level of apoptosis in PC12 cells. As microfluidic systems are advantageous in a range of properties such as throughput and lower use of reagents, they may provide a useful approach for generating <italic>in vitro</italic> models of disease for drug discovery applications.</p></div></front></TEI><pmc article-type="other"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biomicrofluidics</journal-id><journal-title-group><journal-title>Biomicrofluidics</journal-title></journal-title-group><issn pub-type="ppub">1932-1058</issn><issn pub-type="epub">1932-1058</issn><publisher><publisher-name>American Institute of Physics</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21799720</article-id><article-id pub-id-type="pmc">3145239</article-id><article-id pub-id-type="publisher-id">012191BMF</article-id><article-id pub-id-type="doi">10.1063/1.3580756</article-id><article-categories><subj-group subj-group-type="heading"><subject>Special Topic: Microfluidics in Cell Biology and Tissue Engineering (Guest Editor: Ali Khademhosseini)</subject></subj-group></article-categories><title-group><article-title>A microfluidic-based neurotoxin concentration gradient for the generation of an <italic>in vitro</italic> model of Parkinson’s disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Seidi</surname><given-names>Azadeh</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kaji</surname><given-names>Hirokazu</given-names></name><xref ref-type="aff" rid="a2">2</xref><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Annabi</surname><given-names>Nasim</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ostrovidov</surname><given-names>Serge</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ramalingam</surname><given-names>Murugan</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a5">5</xref></contrib><contrib contrib-type="author"><name><surname>Khademhosseini</surname><given-names>Ali</given-names></name><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a2">2</xref><xref ref-type="aff" rid="a6">6</xref><xref ref-type="author-notes" rid="n1">a)</xref></contrib><aff id="a1"><label>1</label>WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan</aff><aff id="a2"><label>2</label>Department of Medicine, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA</aff><aff id="a3"><label>3</label>Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan</aff><aff id="a4"><label>4</label>School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, New South Wales 2006, Australia</aff><aff id="a5"><label>5</label>Faculte de Medecine, National Institute of Health and Medical Research U977, Université de Strasbourg, Strasbourg, Cedex 67085, France</aff><aff id="a6"><label>6</label>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA</aff></contrib-group><author-notes><fn id="n1"><label>a)</label><p>Author to whom correspondence should be addressed. Tel.: +1-617-388-9271. FAX: +1-617-768-8477. Electronic mail: <email>alik@rics.bwh.harvard.edu</email>.</p></fn></author-notes><pub-date pub-type="collection"><month>6</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>29</day><month>6</month><year>2011</year></pub-date><volume>5</volume><issue>2</issue><elocation-id>022214</elocation-id><history><date date-type="received"><day>19</day><month>1</month><year>2011</year></date><date date-type="accepted"><day>30</day><month>3</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011 American Institute of Physics</copyright-statement><copyright-year>2011</copyright-year><copyright-holder>American Institute of Physics</copyright-holder></permissions><abstract><p>In this study, we developed a miniaturized microfluidic-based high-throughput cell toxicity assay to create an <italic>in vitro</italic> model of Parkinson’s disease (PD). In particular, we generated concentration gradients of 6-hydroxydopamine (6-OHDA) to trigger a process of neuronal apoptosis in pheochromocytoma PC12 neuronal cell line. PC12 cells were cultured in a microfluidic channel, and a concentration gradient of 6-OHDA was generated in the channel by using a back and forth movement of the fluid flow. Cellular apoptosis was then analyzed along the channel. The results indicate that at low concentrations of 6-OHDA along the gradient (i.e., approximately less than 260 μM), the neuronal death in the channel was mainly induced by apoptosis, while at higher concentrations, 6-OHDA induced neuronal death mainly through necrosis. Thus, this concentration appears to be useful for creating an <italic>in vitro</italic> model of PD by inducing the highest level of apoptosis in PC12 cells. As microfluidic systems are advantageous in a range of properties such as throughput and lower use of reagents, they may provide a useful approach for generating <italic>in vitro</italic> models of disease for drug discovery applications.</p></abstract><custom-meta-group><custom-meta><meta-name>CCC information</meta-name><meta-value>1932-1058/2011/5(2)/022214/14/$30.00</meta-value></custom-meta><custom-meta><meta-name>sisac</meta-name><meta-value>1932-1058()5:2L.022214;1</meta-value></custom-meta><custom-meta><meta-name>edcode</meta-name><meta-value>MCTE-11013MCTER</meta-value></custom-meta><custom-meta><meta-name>aipkey</meta-name><meta-value>1.3580756</meta-value></custom-meta><custom-meta><meta-name>spin</meta-name><meta-value><named-content content-type="el-docanal"><named-content content-type="att-kind">KK</named-content><named-content content-type="el-pacs"><named-content content-type="att-pacsyr">2011</named-content><named-content content-type="el-pacscode">8785Ox</named-content><named-content content-type="el-pacscode">8719X-</named-content><named-content content-type="el-pacscode">8585+j</named-content></named-content></named-content><named-content content-type="el-jouidx"><named-content content-type="el-country">JP</named-content><named-content content-type="el-totalidx">6</named-content><named-content content-type="el-addidx">bioMEMS</named-content><named-content content-type="el-addidx">cellular biophysics</named-content><named-content content-type="el-addidx">diseases</named-content><named-content content-type="el-addidx">microfluidics</named-content><named-content content-type="el-addidx">neurophysiology</named-content><named-content content-type="el-addidx">physiological models</named-content></named-content></meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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