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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease</title><author><name sortKey="Mendez, Ivar" sort="Mendez, Ivar" uniqKey="Mendez I" first="Ivar" last="Mendez">Ivar Mendez</name><affiliation><nlm:aff id="A1">Dalhousie University and Queen Elizabeth II Health Science Center, Division of Neurosurgery and Neuroscience, Halifax</nlm:aff></affiliation></author><author><name sortKey="Sanchez Pernaute, Rosario" sort="Sanchez Pernaute, Rosario" uniqKey="Sanchez Pernaute R" first="Rosario" last="Sanchez-Pernaute">Rosario Sanchez-Pernaute</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Cooper, Oliver" sort="Cooper, Oliver" uniqKey="Cooper O" first="Oliver" last="Cooper">Oliver Cooper</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Vi Uela, Angel" sort="Vi Uela, Angel" uniqKey="Vi Uela A" first="Angel" last="Vi Uela">Angel Vi Uela</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Ferrari, Daniela" sort="Ferrari, Daniela" uniqKey="Ferrari D" first="Daniela" last="Ferrari">Daniela Ferrari</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Bjorklund, Lars" sort="Bjorklund, Lars" uniqKey="Bjorklund L" first="Lars" last="Björklund">Lars Björklund</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Dagher, Alain" sort="Dagher, Alain" uniqKey="Dagher A" first="Alain" last="Dagher">Alain Dagher</name><affiliation><nlm:aff id="A2">McGill University and Montreal Neurological Institute, McConnel Brain Imaging Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Isacson, Ole" sort="Isacson, Ole" uniqKey="Isacson O" first="Ole" last="Isacson">Ole Isacson</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">15872020</idno><idno type="pmc">2610438</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610438</idno><idno type="RBID">PMC:2610438</idno><idno type="doi">10.1093/brain/awh510</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">000399</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000399</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease</title><author><name sortKey="Mendez, Ivar" sort="Mendez, Ivar" uniqKey="Mendez I" first="Ivar" last="Mendez">Ivar Mendez</name><affiliation><nlm:aff id="A1">Dalhousie University and Queen Elizabeth II Health Science Center, Division of Neurosurgery and Neuroscience, Halifax</nlm:aff></affiliation></author><author><name sortKey="Sanchez Pernaute, Rosario" sort="Sanchez Pernaute, Rosario" uniqKey="Sanchez Pernaute R" first="Rosario" last="Sanchez-Pernaute">Rosario Sanchez-Pernaute</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Cooper, Oliver" sort="Cooper, Oliver" uniqKey="Cooper O" first="Oliver" last="Cooper">Oliver Cooper</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Vi Uela, Angel" sort="Vi Uela, Angel" uniqKey="Vi Uela A" first="Angel" last="Vi Uela">Angel Vi Uela</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Ferrari, Daniela" sort="Ferrari, Daniela" uniqKey="Ferrari D" first="Daniela" last="Ferrari">Daniela Ferrari</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Bjorklund, Lars" sort="Bjorklund, Lars" uniqKey="Bjorklund L" first="Lars" last="Björklund">Lars Björklund</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Dagher, Alain" sort="Dagher, Alain" uniqKey="Dagher A" first="Alain" last="Dagher">Alain Dagher</name><affiliation><nlm:aff id="A2">McGill University and Montreal Neurological Institute, McConnel Brain Imaging Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Isacson, Ole" sort="Isacson, Ole" uniqKey="Isacson O" first="Ole" last="Isacson">Ole Isacson</name><affiliation><nlm:aff id="A3">Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Brain : a journal of neurology</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">We report the first post-mortem analysis of two patients with Parkinson’s disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive <sup>18</sup>F-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (<italic>n</italic> = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type that provides specific dopaminergic innervation to the most affected striatal regions in the parkinsonian brain. Such transplants were able to densely reinnervate the host putamen with new dopamine fibres. The patients received only 6 months of standard immune suppression, yet by post-mortem analysis 3–4 years after surgery the transplants appeared only mildly immunogenic to the host brain, by analysis of microglial CD45 and CD68 markers. This study demonstrates that, using these methods, dopamine neuronal replacement cell therapy can be beneficial for patients with advanced disease, and that changing technical approaches could have a favourable impact on efficacy and adverse events following neural transplantation.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0372537</journal-id><journal-id journal-id-type="pubmed-jr-id">1917</journal-id><journal-id journal-id-type="nlm-ta">Brain</journal-id><journal-title>Brain : a journal of neurology</journal-title><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn></journal-meta><article-meta><article-id pub-id-type="pmid">15872020</article-id><article-id pub-id-type="pmc">2610438</article-id><article-id pub-id-type="doi">10.1093/brain/awh510</article-id><article-id pub-id-type="manuscript">NIHMS81627</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mendez</surname><given-names>Ivar</given-names></name><xref rid="A1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Sanchez-Pernaute</surname><given-names>Rosario</given-names></name><xref rid="A3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Cooper</surname><given-names>Oliver</given-names></name><xref rid="A3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Viñuela</surname><given-names>Angel</given-names></name><xref rid="A3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Ferrari</surname><given-names>Daniela</given-names></name><xref rid="A3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Björklund</surname><given-names>Lars</given-names></name><xref rid="A3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Dagher</surname><given-names>Alain</given-names></name><xref rid="A2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Isacson</surname><given-names>Ole</given-names></name><xref rid="A3" ref-type="aff">3</xref></contrib></contrib-group><aff id="A1"><label>1</label>Dalhousie University and Queen Elizabeth II Health Science Center, Division of Neurosurgery and Neuroscience, Halifax</aff><aff id="A2"><label>2</label>McGill University and Montreal Neurological Institute, McConnel Brain Imaging Centre, Montreal, Canada</aff><aff id="A3"><label>3</label>Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Belmont, MA, USA</aff><author-notes><corresp id="FN1">Correspondence to: Professor Ole Isacson, Neuroregeneration Laboratory, Harvard Medical School, McLean Hospital, MRC 130, 115 Mill St, Belmont, MA 02478, USA, E-mail: <email>isacson@hms.harvard.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>5</day><month>12</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>4</day><month>5</month><year>2005</year></pub-date><pub-date pub-type="ppub"><month>7</month><year>2005</year></pub-date><pub-date pub-type="pmc-release"><day>29</day><month>12</month><year>2008</year></pub-date><volume>128</volume><issue>Pt 7</issue><fpage>1498</fpage><lpage>1510</lpage><related-article journal-id-type="nlm-ta" journal-id="Brain" related-article-type="commentary" page="1478" id="N0x19cac40N0x2861bd8" xlink:href="15980119" ext-link-type="pubmed" vol="128"></related-article><abstract><p id="P1">We report the first post-mortem analysis of two patients with Parkinson’s disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive <sup>18</sup>F-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (<italic>n</italic> = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type that provides specific dopaminergic innervation to the most affected striatal regions in the parkinsonian brain. Such transplants were able to densely reinnervate the host putamen with new dopamine fibres. The patients received only 6 months of standard immune suppression, yet by post-mortem analysis 3–4 years after surgery the transplants appeared only mildly immunogenic to the host brain, by analysis of microglial CD45 and CD68 markers. This study demonstrates that, using these methods, dopamine neuronal replacement cell therapy can be beneficial for patients with advanced disease, and that changing technical approaches could have a favourable impact on efficacy and adverse events following neural transplantation.</p></abstract><kwd-group><kwd>transplantation</kwd><kwd>dopamine neuron</kwd><kwd>Parkinson’s disease</kwd></kwd-group><contract-num rid="NS1">P50 NS039793-06A10005</contract-num><contract-sponsor id="NS1">National Institute of Neurological Disorders and Stroke : NINDS</contract-sponsor></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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