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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells</title><author><name sortKey="Redmond, D Eugene" sort="Redmond, D Eugene" uniqKey="Redmond D" first="D. Eugene" last="Redmond">D. Eugene Redmond</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurosurgery</nlm:aff></affiliation></author><author><name sortKey="Bjugstad, Kimberly B" sort="Bjugstad, Kimberly B" uniqKey="Bjugstad K" first="Kimberly B." last="Bjugstad">Kimberly B. Bjugstad</name><affiliation><nlm:aff id="aff4">Department of Psychiatry, University of Colorado, Aurora, CO 80045;</nlm:aff></affiliation></author><author><name sortKey="Teng, Yang D" sort="Teng, Yang D" uniqKey="Teng Y" first="Yang D." last="Teng">Yang D. Teng</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Ourednik, Vaclav" sort="Ourednik, Vaclav" uniqKey="Ourednik V" first="Vaclav" last="Ourednik">Vaclav Ourednik</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Ourednik, Jitka" sort="Ourednik, Jitka" uniqKey="Ourednik J" first="Jitka" last="Ourednik">Jitka Ourednik</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Wakeman, Dustin R" sort="Wakeman, Dustin R" uniqKey="Wakeman D" first="Dustin R." last="Wakeman">Dustin R. Wakeman</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">Biomedical Sciences and Molecular Pathology Programs, University of California at San Diego, La Jolla, CA 92093</nlm:aff></affiliation></author><author><name sortKey="Parsons, Xuejun H" sort="Parsons, Xuejun H" uniqKey="Parsons X" first="Xuejun H." last="Parsons">Xuejun H. Parsons</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author><author><name sortKey="Gonzalez, Rodolfo" sort="Gonzalez, Rodolfo" uniqKey="Gonzalez R" first="Rodolfo" last="Gonzalez">Rodolfo Gonzalez</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">Biomedical Sciences and Molecular Pathology Programs, University of California at San Diego, La Jolla, CA 92093</nlm:aff></affiliation></author><author><name sortKey="Blanchard, Barbara C" sort="Blanchard, Barbara C" uniqKey="Blanchard B" first="Barbara C." last="Blanchard">Barbara C. Blanchard</name><affiliation><nlm:aff id="aff4">Department of Psychiatry, University of Colorado, Aurora, CO 80045;</nlm:aff></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation><nlm:aff wicri:cut="; and" id="aff7">Department of Neurology, University of British Columbia, Vancouver, BC, Canada V6T 2B5</nlm:aff></affiliation></author><author><name sortKey="Gu, Zezong" sort="Gu, Zezong" uniqKey="Gu Z" first="Zezong" last="Gu">Zezong Gu</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author><author><name sortKey="Lipton, Stuart A" sort="Lipton, Stuart A" uniqKey="Lipton S" first="Stuart A." last="Lipton">Stuart A. Lipton</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author><author><name sortKey="Markakis, Eleni A" sort="Markakis, Eleni A" uniqKey="Markakis E" first="Eleni A." last="Markakis">Eleni A. Markakis</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation></author><author><name sortKey="Roth, Robert H" sort="Roth, Robert H" uniqKey="Roth R" first="Robert H." last="Roth">Robert H. Roth</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Pharmacology, Yale University School of Medicine, New Haven, CT 06510;</nlm:aff></affiliation></author><author><name sortKey="Elsworth, John D" sort="Elsworth, John D" uniqKey="Elsworth J" first="John D." last="Elsworth">John D. Elsworth</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Pharmacology, Yale University School of Medicine, New Haven, CT 06510;</nlm:aff></affiliation></author><author><name sortKey="Sladek, John R" sort="Sladek, John R" uniqKey="Sladek J" first="John R." last="Sladek">John R. Sladek</name><affiliation><nlm:aff id="aff4">Department of Psychiatry, University of Colorado, Aurora, CO 80045;</nlm:aff></affiliation></author><author><name sortKey="Sidman, Richard L" sort="Sidman, Richard L" uniqKey="Sidman R" first="Richard L." last="Sidman">Richard L. Sidman</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Snyder, Evan Y" sort="Snyder, Evan Y" uniqKey="Snyder E" first="Evan Y." last="Snyder">Evan Y. Snyder</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17586681</idno><idno type="pmc">1896134</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1896134</idno><idno type="RBID">PMC:1896134</idno><idno type="doi">10.1073/pnas.0704091104</idno><date when="2007">2007</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">Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells</title><author><name sortKey="Redmond, D Eugene" sort="Redmond, D Eugene" uniqKey="Redmond D" first="D. Eugene" last="Redmond">D. Eugene Redmond</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurosurgery</nlm:aff></affiliation></author><author><name sortKey="Bjugstad, Kimberly B" sort="Bjugstad, Kimberly B" uniqKey="Bjugstad K" first="Kimberly B." last="Bjugstad">Kimberly B. Bjugstad</name><affiliation><nlm:aff id="aff4">Department of Psychiatry, University of Colorado, Aurora, CO 80045;</nlm:aff></affiliation></author><author><name sortKey="Teng, Yang D" sort="Teng, Yang D" uniqKey="Teng Y" first="Yang D." last="Teng">Yang D. Teng</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Ourednik, Vaclav" sort="Ourednik, Vaclav" uniqKey="Ourednik V" first="Vaclav" last="Ourednik">Vaclav Ourednik</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Ourednik, Jitka" sort="Ourednik, Jitka" uniqKey="Ourednik J" first="Jitka" last="Ourednik">Jitka Ourednik</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Wakeman, Dustin R" sort="Wakeman, Dustin R" uniqKey="Wakeman D" first="Dustin R." last="Wakeman">Dustin R. Wakeman</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">Biomedical Sciences and Molecular Pathology Programs, University of California at San Diego, La Jolla, CA 92093</nlm:aff></affiliation></author><author><name sortKey="Parsons, Xuejun H" sort="Parsons, Xuejun H" uniqKey="Parsons X" first="Xuejun H." last="Parsons">Xuejun H. Parsons</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author><author><name sortKey="Gonzalez, Rodolfo" sort="Gonzalez, Rodolfo" uniqKey="Gonzalez R" first="Rodolfo" last="Gonzalez">Rodolfo Gonzalez</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">Biomedical Sciences and Molecular Pathology Programs, University of California at San Diego, La Jolla, CA 92093</nlm:aff></affiliation></author><author><name sortKey="Blanchard, Barbara C" sort="Blanchard, Barbara C" uniqKey="Blanchard B" first="Barbara C." last="Blanchard">Barbara C. Blanchard</name><affiliation><nlm:aff id="aff4">Department of Psychiatry, University of Colorado, Aurora, CO 80045;</nlm:aff></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation><nlm:aff wicri:cut="; and" id="aff7">Department of Neurology, University of British Columbia, Vancouver, BC, Canada V6T 2B5</nlm:aff></affiliation></author><author><name sortKey="Gu, Zezong" sort="Gu, Zezong" uniqKey="Gu Z" first="Zezong" last="Gu">Zezong Gu</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author><author><name sortKey="Lipton, Stuart A" sort="Lipton, Stuart A" uniqKey="Lipton S" first="Stuart A." last="Lipton">Stuart A. Lipton</name><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author><author><name sortKey="Markakis, Eleni A" sort="Markakis, Eleni A" uniqKey="Markakis E" first="Eleni A." last="Markakis">Eleni A. Markakis</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation></author><author><name sortKey="Roth, Robert H" sort="Roth, Robert H" uniqKey="Roth R" first="Robert H." last="Roth">Robert H. Roth</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Pharmacology, Yale University School of Medicine, New Haven, CT 06510;</nlm:aff></affiliation></author><author><name sortKey="Elsworth, John D" sort="Elsworth, John D" uniqKey="Elsworth J" first="John D." last="Elsworth">John D. Elsworth</name><affiliation><nlm:aff id="aff1">Departments of *Psychiatry,</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Pharmacology, Yale University School of Medicine, New Haven, CT 06510;</nlm:aff></affiliation></author><author><name sortKey="Sladek, John R" sort="Sladek, John R" uniqKey="Sladek J" first="John R." last="Sladek">John R. Sladek</name><affiliation><nlm:aff id="aff4">Department of Psychiatry, University of Colorado, Aurora, CO 80045;</nlm:aff></affiliation></author><author><name sortKey="Sidman, Richard L" sort="Sidman, Richard L" uniqKey="Sidman R" first="Richard L." last="Sidman">Richard L. Sidman</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Snyder, Evan Y" sort="Snyder, Evan Y" uniqKey="Snyder E" first="Evan Y." last="Snyder">Evan Y. Snyder</name><affiliation><nlm:aff id="aff5">Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Stem cells have been widely assumed to be capable of replacing lost or damaged cells in a number of diseases, including Parkinson's disease (PD), in which neurons of the substantia nigra (SN) die and fail to provide the neurotransmitter, dopamine (DA), to the striatum. We report that undifferentiated human neural stem cells (hNSCs) implanted into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Parkinsonian primates survived, migrated, and had a functional impact as assessed quantitatively by behavioral improvement in this DA-deficit model, in which Parkinsonian signs directly correlate to reduced DA levels. A small number of hNSC progeny differentiated into tyrosine hydroxylase (TH) and/or dopamine transporter (DAT) immunopositive cells, suggesting that the microenvironment within and around the lesioned adult host SN still permits development of a DA phenotype by responsive progenitor cells. A much larger number of hNSC-derived cells that did not express neuronal or DA markers was found arrayed along the persisting nigrostriatal path, juxtaposed with host cells. These hNSCs, which express DA-protective factors, were therefore well positioned to influence host TH+ cells and mediate other homeostatic adjustments, as reflected in a return to baseline endogenous neuronal number-to-size ratios, preservation of extant host nigrostriatal circuitry, and a normalizing effect on α-synuclein aggregation. We propose that multiple modes of reciprocal interaction between exogenous hNSCs and the pathological host milieu underlie the functional improvement observed in this model of PD.</p></div></front></TEI><pmc article-type="research-article"><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">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17586681</article-id><article-id pub-id-type="pmc">1896134</article-id><article-id pub-id-type="publisher-id">6665</article-id><article-id pub-id-type="doi">10.1073/pnas.0704091104</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Neuroscience</subject></subj-group></subj-group><series-title>From the Cover</series-title></article-categories><title-group><article-title>Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Redmond</surname><given-names>D. Eugene</given-names><suffix>Jr.</suffix></name><xref rid="aff1" ref-type="aff">*</xref><xref rid="aff2" ref-type="aff"><sup>†</sup></xref><xref ref-type="corresp" rid="cor1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bjugstad</surname><given-names>Kimberly B.</given-names></name><xref rid="aff4" ref-type="aff"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Teng</surname><given-names>Yang D.</given-names></name><xref rid="aff5" ref-type="aff"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ourednik</surname><given-names>Vaclav</given-names></name><xref rid="aff5" ref-type="aff"><sup>¶</sup></xref><xref rid="FN1" ref-type="author-notes"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ourednik</surname><given-names>Jitka</given-names></name><xref rid="aff5" ref-type="aff"><sup>¶</sup></xref><xref rid="FN1" ref-type="author-notes"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wakeman</surname><given-names>Dustin R.</given-names></name><xref rid="aff6" ref-type="aff">**</xref><xref rid="aff8" ref-type="aff"><sup>††</sup></xref></contrib><contrib contrib-type="author"><name><surname>Parsons</surname><given-names>Xuejun H.</given-names></name><xref rid="aff6" ref-type="aff">**</xref></contrib><contrib contrib-type="author"><name><surname>Gonzalez</surname><given-names>Rodolfo</given-names></name><xref rid="aff6" ref-type="aff">**</xref><xref rid="aff8" ref-type="aff"><sup>††</sup></xref></contrib><contrib contrib-type="author"><name><surname>Blanchard</surname><given-names>Barbara C.</given-names></name><xref rid="aff4" ref-type="aff"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Seung U.</given-names></name><xref rid="aff7" ref-type="aff"><sup>‡‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gu</surname><given-names>Zezong</given-names></name><xref rid="aff6" ref-type="aff">**</xref></contrib><contrib contrib-type="author"><name><surname>Lipton</surname><given-names>Stuart A.</given-names></name><xref rid="aff6" ref-type="aff">**</xref></contrib><contrib contrib-type="author"><name><surname>Markakis</surname><given-names>Eleni A.</given-names></name><xref rid="aff1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Roth</surname><given-names>Robert H.</given-names></name><xref rid="aff1" ref-type="aff">*</xref><xref rid="aff3" ref-type="aff"><sup>§§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Elsworth</surname><given-names>John D.</given-names></name><xref rid="aff1" ref-type="aff">*</xref><xref rid="aff3" ref-type="aff"><sup>§§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sladek</surname><given-names>John R.</given-names><suffix>Jr.</suffix></name><xref rid="aff4" ref-type="aff"><sup>§</sup></xref><xref rid="FN2" ref-type="author-notes"><sup>¶¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sidman</surname><given-names>Richard L.</given-names></name><xref ref-type="corresp" rid="cor1"><sup>‡</sup></xref><xref rid="aff5" ref-type="aff"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Snyder</surname><given-names>Evan Y.</given-names></name><xref ref-type="corresp" rid="cor1"><sup>‡</sup></xref><xref rid="aff5" ref-type="aff"><sup>¶</sup></xref><xref rid="aff6" ref-type="aff">**</xref></contrib><aff id="aff1">Departments of *Psychiatry,</aff><aff id="aff2"><sup>†</sup>Neurosurgery, and</aff><aff id="aff3"><sup>§§</sup>Pharmacology, Yale University School of Medicine, New Haven, CT 06510;</aff><aff id="aff4"><sup>§</sup>Department of Psychiatry, University of Colorado, Aurora, CO 80045;</aff><aff id="aff5"><sup>¶</sup>Departments of Neurology and Neurosurgery, Harvard Medical School, Children's Hospital and Beth Israel Deaconess Medical Center, Division of Spinal Cord Injury Research, Veterans Affairs Boston Healthcare System, Boston, MA 02115;</aff><aff id="aff6">**Burnham Institute for Medical Research, La Jolla, CA 92037;</aff><aff id="aff7"><sup>‡‡</sup>Department of Neurology, University of British Columbia, Vancouver, BC, Canada V6T 2B5; and</aff><aff id="aff8"><sup>††</sup>Biomedical Sciences and Molecular Pathology Programs, University of California at San Diego, La Jolla, CA 92093</aff></contrib-group><author-notes><corresp id="cor1"><sup>‡</sup>To whom correspondence may be addressed. E-mail: <email>eugene.redmond@yale.edu</email>, <email>richard_sidman@hms.harvard.edu</email>, or <email>esnyder@burnham.org</email></corresp><fn fn-type="con"><p>Contributed by Richard L. Sidman, May 2, 2007</p></fn><fn fn-type="con"><p>Author contributions: D.E.R., K.B.B., Y.D.T., and V.O. contributed equally to this work; D.E.R., Y.D.T., V.O., R.H.R., J.D.E., J.R.S., R.L.S., and E.Y.S. designed research; D.E.R., K.B.B., Y.D.T., V.O., J.O., D.R.W., X.H.P., R.G., B.C.B., Z.G., S.A.L., E.A.M., J.D.E., and E.Y.S. performed research; S.U.K. contributed new reagents/analytic tools; D.E.R., K.B.B., Y.D.T., V.O., J.O., D.R.W., X.H.P., R.G., B.C.B., Z.G., S.A.L., E.A.M., R.H.R., J.D.E., J.R.S., R.L.S., and E.Y.S. analyzed data; and D.E.R., K.B.B., Y.D.T., R.L.S., and E.Y.S. wrote the paper.</p></fn><fn fn-type="present-address" id="FN1"><p><sup>‖</sup>Present address: Laboratory of CNS Development, Regeneration, and Neurotransplantation, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250.</p></fn><fn fn-type="present-address" id="FN2"><p><sup>¶¶</sup>Present address: Department of Biology, California Lutheran University, 60 West Olsen Road, Thousand Oaks, CA 91360.</p></fn></author-notes><pub-date pub-type="ppub"><day>17</day><month>7</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>22</day><month>6</month><year>2007</year></pub-date><volume>104</volume><issue>29</issue><fpage>12175</fpage><lpage>12180</lpage><history><date date-type="received"><day>6</day><month>3</month><year>2007</year></date></history><copyright-statement>© 2007 by The National Academy of Sciences of the USA</copyright-statement><copyright-year>2007</copyright-year><license license-type="open-access"><p>Freely available online through the PNAS open access option.</p></license><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq02907012175.pdf"></self-uri><abstract><p>Stem cells have been widely assumed to be capable of replacing lost or damaged cells in a number of diseases, including Parkinson's disease (PD), in which neurons of the substantia nigra (SN) die and fail to provide the neurotransmitter, dopamine (DA), to the striatum. We report that undifferentiated human neural stem cells (hNSCs) implanted into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Parkinsonian primates survived, migrated, and had a functional impact as assessed quantitatively by behavioral improvement in this DA-deficit model, in which Parkinsonian signs directly correlate to reduced DA levels. A small number of hNSC progeny differentiated into tyrosine hydroxylase (TH) and/or dopamine transporter (DAT) immunopositive cells, suggesting that the microenvironment within and around the lesioned adult host SN still permits development of a DA phenotype by responsive progenitor cells. A much larger number of hNSC-derived cells that did not express neuronal or DA markers was found arrayed along the persisting nigrostriatal path, juxtaposed with host cells. These hNSCs, which express DA-protective factors, were therefore well positioned to influence host TH+ cells and mediate other homeostatic adjustments, as reflected in a return to baseline endogenous neuronal number-to-size ratios, preservation of extant host nigrostriatal circuitry, and a normalizing effect on α-synuclein aggregation. We propose that multiple modes of reciprocal interaction between exogenous hNSCs and the pathological host milieu underlie the functional improvement observed in this model of PD.</p></abstract><kwd-group><kwd>1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine</kwd><kwd>dopamine</kwd><kwd>Parkinson's disease</kwd><kwd>synuclein</kwd><kwd>tyrosine hydroxylase</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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