Multitracer assessment of dopamine function after transplantation of embryonic stem cell‐derived neural stem cells in a primate model of Parkinson's disease
Identifieur interne : 002184 ( Main/Corpus ); précédent : 002183; suivant : 002185Multitracer assessment of dopamine function after transplantation of embryonic stem cell‐derived neural stem cells in a primate model of Parkinson's disease
Auteurs : Shin-Ichi Muramatsu ; Tsuyoshi Okuno ; Yutaka Suzuki ; Takashi Nakayama ; Takeharu Kakiuchi ; Naomi Takino ; Asako Iida ; Fumiko Ono ; Keiji Terao ; Nobuo Inoue ; Imaharu Nakano ; Yasushi Kondo ; Hideo TsukadaSource :
- Synapse [ 0887-4476 ] ; 2009-07.
English descriptors
Abstract
The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)‐synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M‐1 and M‐2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA‐specific functions, we used multiple [11C]‐labeled positron emission tomography (PET) tracers, including [β‐11C]L‐3,4‐dihydroxyphenylalanine (L‐[β‐11C]DOPA, DA precursor ligand), [11C]‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([11C]β‐CFT, DA transporter ligand) and [11C]raclopride (D2 receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of L‐[β‐11C]DOPA (M‐1:41%, M‐2:61%) and [11C]β‐CFT (M‐1:31%, M‐2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M‐2 induced reduced [11C]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell‐based therapies against PD. Synapse 63: 541‐548, 2009. © 2009 Wiley‐Liss, Inc.
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DOI: 10.1002/syn.20634
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Japan</mods:affiliation></affiliation></author><author><name sortKey="Okuno, Tsuyoshi" sort="Okuno, Tsuyoshi" uniqKey="Okuno T" first="Tsuyoshi" last="Okuno">Tsuyoshi Okuno</name><affiliation><mods:affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</mods:affiliation></affiliation></author><author><name sortKey="Suzuki, Yutaka" sort="Suzuki, Yutaka" uniqKey="Suzuki Y" first="Yutaka" last="Suzuki">Yutaka Suzuki</name><affiliation><mods:affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</mods:affiliation></affiliation></author><author><name sortKey="Nakayama, Takashi" sort="Nakayama, Takashi" uniqKey="Nakayama T" first="Takashi" last="Nakayama">Takashi Nakayama</name><affiliation><mods:affiliation>Department of Biochemistry I, Yokohama City University School of Medicine, Kanagawa 236‐0004, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kakiuchi, Takeharu" sort="Kakiuchi, Takeharu" uniqKey="Kakiuchi T" first="Takeharu" last="Kakiuchi">Takeharu Kakiuchi</name><affiliation><mods:affiliation>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</mods:affiliation></affiliation></author><author><name sortKey="Takino, Naomi" sort="Takino, Naomi" uniqKey="Takino N" first="Naomi" last="Takino">Naomi Takino</name><affiliation><mods:affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</mods:affiliation></affiliation></author><author><name sortKey="Iida, Asako" sort="Iida, Asako" uniqKey="Iida A" first="Asako" last="Iida">Asako Iida</name><affiliation><mods:affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</mods:affiliation></affiliation></author><author><name sortKey="Ono, Fumiko" sort="Ono, Fumiko" uniqKey="Ono F" first="Fumiko" last="Ono">Fumiko Ono</name><affiliation><mods:affiliation>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</mods:affiliation></affiliation></author><author><name sortKey="Terao, Keiji" sort="Terao, Keiji" uniqKey="Terao K" first="Keiji" last="Terao">Keiji Terao</name><affiliation><mods:affiliation>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</mods:affiliation></affiliation></author><author><name sortKey="Inoue, Nobuo" sort="Inoue, Nobuo" uniqKey="Inoue N" first="Nobuo" last="Inoue">Nobuo Inoue</name><affiliation><mods:affiliation>Division of Regenerative Neurosciences, Tokyo Metropolitan University, Tokyo 116‐8551, Japan</mods:affiliation></affiliation></author><author><name sortKey="Nakano, Imaharu" sort="Nakano, Imaharu" uniqKey="Nakano I" first="Imaharu" last="Nakano">Imaharu Nakano</name><affiliation><mods:affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kondo, Yasushi" sort="Kondo, Yasushi" uniqKey="Kondo Y" first="Yasushi" last="Kondo">Yasushi Kondo</name><affiliation><mods:affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tsukada, Hideo" sort="Tsukada, Hideo" uniqKey="Tsukada H" first="Hideo" last="Tsukada">Hideo Tsukada</name><affiliation><mods:affiliation>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="ISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-07">2009-07</date><biblScope unit="volume">63</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="541">541</biblScope><biblScope unit="page" to="548">548</biblScope></imprint><idno type="ISSN">0887-4476</idno></series><idno type="istex">493F050D7EAA94FFA13E53E2530CA3D2352717FA</idno><idno type="DOI">10.1002/syn.20634</idno><idno type="ArticleID">SYN20634</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0887-4476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ES cell</term><term>MPTP</term><term>PET</term><term>monkey</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)‐synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M‐1 and M‐2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA‐specific functions, we used multiple [11C]‐labeled positron emission tomography (PET) tracers, including [β‐11C]L‐3,4‐dihydroxyphenylalanine (L‐[β‐11C]DOPA, DA precursor ligand), [11C]‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([11C]β‐CFT, DA transporter ligand) and [11C]raclopride (D2 receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of L‐[β‐11C]DOPA (M‐1:41%, M‐2:61%) and [11C]β‐CFT (M‐1:31%, M‐2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M‐2 induced reduced [11C]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell‐based therapies against PD. Synapse 63: 541‐548, 2009. © 2009 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Shin‐Ichi Muramatsu</name><affiliations><json:string>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</json:string></affiliations></json:item><json:item><name>Tsuyoshi Okuno</name><affiliations><json:string>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</json:string></affiliations></json:item><json:item><name>Yutaka Suzuki</name><affiliations><json:string>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</json:string></affiliations></json:item><json:item><name>Takashi Nakayama</name><affiliations><json:string>Department of Biochemistry I, Yokohama City University School of Medicine, Kanagawa 236‐0004, Japan</json:string></affiliations></json:item><json:item><name>Takeharu Kakiuchi</name><affiliations><json:string>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</json:string></affiliations></json:item><json:item><name>Naomi Takino</name><affiliations><json:string>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</json:string></affiliations></json:item><json:item><name>Asako Iida</name><affiliations><json:string>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</json:string></affiliations></json:item><json:item><name>Fumiko Ono</name><affiliations><json:string>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</json:string></affiliations></json:item><json:item><name>Keiji Terao</name><affiliations><json:string>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</json:string></affiliations></json:item><json:item><name>Nobuo Inoue</name><affiliations><json:string>Division of Regenerative Neurosciences, Tokyo Metropolitan University, Tokyo 116‐8551, Japan</json:string></affiliations></json:item><json:item><name>Imaharu Nakano</name><affiliations><json:string>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</json:string></affiliations></json:item><json:item><name>Yasushi Kondo</name><affiliations><json:string>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</json:string></affiliations></json:item><json:item><name>Hideo Tsukada</name><affiliations><json:string>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>ES cell</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PET</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>monkey</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MPTP</value></json:item></subject><articleId><json:string>SYN20634</json:string></articleId><language><json:string>eng</json:string></language><abstract>The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)‐synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M‐1 and M‐2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA‐specific functions, we used multiple [11C]‐labeled positron emission tomography (PET) tracers, including [β‐11C]L‐3,4‐dihydroxyphenylalanine (L‐[β‐11C]DOPA, DA precursor ligand), [11C]‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([11C]β‐CFT, DA transporter ligand) and [11C]raclopride (D2 receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of L‐[β‐11C]DOPA (M‐1:41%, M‐2:61%) and [11C]β‐CFT (M‐1:31%, M‐2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M‐2 induced reduced [11C]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell‐based therapies against PD. Synapse 63: 541‐548, 2009. © 2009 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>6.92</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>1580</abstractCharCount><pdfWordCount>4376</pdfWordCount><pdfCharCount>28496</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>212</abstractWordCount></qualityIndicators><title>Multitracer assessment of dopamine function after transplantation of embryonic stem cell‐derived neural stem cells in a primate model of Parkinson's disease</title><genre><json:string>article</json:string></genre><host><volume>63</volume><publisherId><json:string>SYN</json:string></publisherId><pages><total>8</total><last>548</last><first>541</first></pages><issn><json:string>0887-4476</json:string></issn><issue>7</issue><subject><json:item><value>Research 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type="main" xml:lang="en">Multitracer assessment of dopamine function after transplantation of embryonic stem cell‐derived neural stem cells in a primate model of Parkinson's disease</title><author><persName><forename type="first">Shin‐Ichi</forename><surname>Muramatsu</surname></persName><note type="correspondence"><p>Correspondence: Division of Neurology, Department of Medicine, Jichi Medical University, 3311‐1 Yakushiji, Shimotsuke, Tochigi 329‐0498, Japan</p></note><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation></author><author><persName><forename type="first">Tsuyoshi</forename><surname>Okuno</surname></persName><affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</affiliation></author><author><persName><forename type="first">Yutaka</forename><surname>Suzuki</surname></persName><affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</affiliation></author><author><persName><forename type="first">Takashi</forename><surname>Nakayama</surname></persName><affiliation>Department of Biochemistry I, Yokohama City University School of Medicine, Kanagawa 236‐0004, Japan</affiliation></author><author><persName><forename type="first">Takeharu</forename><surname>Kakiuchi</surname></persName><affiliation>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</affiliation></author><author><persName><forename type="first">Naomi</forename><surname>Takino</surname></persName><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation></author><author><persName><forename type="first">Asako</forename><surname>Iida</surname></persName><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation></author><author><persName><forename type="first">Fumiko</forename><surname>Ono</surname></persName><affiliation>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</affiliation></author><author><persName><forename type="first">Keiji</forename><surname>Terao</surname></persName><affiliation>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</affiliation></author><author><persName><forename type="first">Nobuo</forename><surname>Inoue</surname></persName><affiliation>Division of Regenerative Neurosciences, Tokyo Metropolitan University, Tokyo 116‐8551, Japan</affiliation></author><author><persName><forename type="first">Imaharu</forename><surname>Nakano</surname></persName><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation></author><author><persName><forename type="first">Yasushi</forename><surname>Kondo</surname></persName><affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</affiliation></author><author><persName><forename type="first">Hideo</forename><surname>Tsukada</surname></persName><affiliation>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</affiliation></author></analytic><monogr><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="pISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><idno type="DOI">10.1002/(ISSN)1098-2396</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-07"></date><biblScope unit="volume">63</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="541">541</biblScope><biblScope unit="page" to="548">548</biblScope></imprint></monogr><idno type="istex">493F050D7EAA94FFA13E53E2530CA3D2352717FA</idno><idno type="DOI">10.1002/syn.20634</idno><idno type="ArticleID">SYN20634</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)‐synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M‐1 and M‐2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA‐specific functions, we used multiple [11C]‐labeled positron emission tomography (PET) tracers, including [β‐11C]L‐3,4‐dihydroxyphenylalanine (L‐[β‐11C]DOPA, DA precursor ligand), [11C]‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([11C]β‐CFT, DA transporter ligand) and [11C]raclopride (D2 receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of L‐[β‐11C]DOPA (M‐1:41%, M‐2:61%) and [11C]β‐CFT (M‐1:31%, M‐2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M‐2 induced reduced [11C]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell‐based therapies against PD. Synapse 63: 541‐548, 2009. © 2009 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>ES cell</term></item><item><term>PET</term></item><item><term>monkey</term></item><item><term>MPTP</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-08-18">Received</change><change when="2008-10-31">Registration</change><change when="2009-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/493F050D7EAA94FFA13E53E2530CA3D2352717FA/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" 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creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Shin‐Ichi</givenNames><familyName>Muramatsu</familyName></personName><contactDetails><email>muramats@ms.jichi.ac.jp</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Tsuyoshi</givenNames><familyName>Okuno</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Yutaka</givenNames><familyName>Suzuki</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Takashi</givenNames><familyName>Nakayama</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Takeharu</givenNames><familyName>Kakiuchi</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Naomi</givenNames><familyName>Takino</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Asako</givenNames><familyName>Iida</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Fumiko</givenNames><familyName>Ono</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Keiji</givenNames><familyName>Terao</familyName></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Nobuo</givenNames><familyName>Inoue</familyName></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Imaharu</givenNames><familyName>Nakano</familyName></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Yasushi</givenNames><familyName>Kondo</familyName></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Hideo</givenNames><familyName>Tsukada</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="JP" type="organization"><unparsedAffiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="JP" type="organization"><unparsedAffiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="JP" type="organization"><unparsedAffiliation>Department of Biochemistry I, Yokohama City University School of Medicine, Kanagawa 236‐0004, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="JP" type="organization"><unparsedAffiliation>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="JP" type="organization"><unparsedAffiliation>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="JP" type="organization"><unparsedAffiliation>Division of Regenerative Neurosciences, Tokyo Metropolitan University, Tokyo 116‐8551, Japan</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">ES cell</keyword><keyword xml:id="kwd2">PET</keyword><keyword xml:id="kwd3">monkey</keyword><keyword xml:id="kwd4">MPTP</keyword></keywordGroup><fundingInfo><fundingAgency>Ministry of Health, Labor and Welfare of Japan</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Ministry of Education, Culture, Sports, Science and Technology of Japan (Special Coordination Funds)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Japan Society for the Promotion of Science (Grant‐in‐Aid for Creative Scientific Research)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>CREST</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Japan Science and Technology Agency (JST)</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)‐synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M‐1 and M‐2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA‐specific functions, we used multiple [<sup>11</sup>C]‐labeled positron emission tomography (PET) tracers, including [β‐<sup>11</sup>C]<sc>L</sc>‐3,4‐dihydroxyphenylalanine (<sc>L</sc>‐[β‐<sup>11</sup>C]DOPA, DA precursor ligand), [<sup>11</sup>C]‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([<sup>11</sup>C]β‐CFT, DA transporter ligand) and [<sup>11</sup>C]raclopride (D<sub>2</sub> receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of <sc>L</sc>‐[β‐<sup>11</sup>C]DOPA (M‐1:41%, M‐2:61%) and [<sup>11</sup>C]β‐CFT (M‐1:31%, M‐2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M‐2 induced reduced [<sup>11</sup>C]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell‐based therapies against PD. Synapse 63: 541‐548, 2009. © 2009 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Multitracer assessment of dopamine function after transplantation of embryonic stem cell‐derived neural stem cells in a primate model of Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Graft Assessment in PD Monkey</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Multitracer assessment of dopamine function after transplantation of embryonic stem cell‐derived neural stem cells in a primate model of Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Shin‐Ichi</namePart><namePart type="family">Muramatsu</namePart><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation><description>Correspondence: Division of Neurology, Department of Medicine, Jichi Medical University, 3311‐1 Yakushiji, Shimotsuke, Tochigi 329‐0498, Japan</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tsuyoshi</namePart><namePart type="family">Okuno</namePart><affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yutaka</namePart><namePart type="family">Suzuki</namePart><affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Takashi</namePart><namePart type="family">Nakayama</namePart><affiliation>Department of Biochemistry I, Yokohama City University School of Medicine, Kanagawa 236‐0004, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Takeharu</namePart><namePart type="family">Kakiuchi</namePart><affiliation>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Naomi</namePart><namePart type="family">Takino</namePart><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Asako</namePart><namePart type="family">Iida</namePart><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Fumiko</namePart><namePart type="family">Ono</namePart><affiliation>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Keiji</namePart><namePart type="family">Terao</namePart><affiliation>Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305‐0843, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nobuo</namePart><namePart type="family">Inoue</namePart><affiliation>Division of Regenerative Neurosciences, Tokyo Metropolitan University, Tokyo 116‐8551, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Imaharu</namePart><namePart type="family">Nakano</namePart><affiliation>Divison of Neurology, Department of Medicine, Jichi Medical University, Tochigi 329‐0498, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yasushi</namePart><namePart type="family">Kondo</namePart><affiliation>Mitsubishi Tanabe Pharma Corporation, Osaka 532‐8505, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hideo</namePart><namePart type="family">Tsukada</namePart><affiliation>Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434‐8601, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2009-07</dateIssued><dateCaptured encoding="w3cdtf">2008-08-18</dateCaptured><dateValid encoding="w3cdtf">2008-10-31</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="references">28</extent><extent unit="words">980</extent></physicalDescription><abstract lang="en">The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)‐synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M‐1 and M‐2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA‐specific functions, we used multiple [11C]‐labeled positron emission tomography (PET) tracers, including [β‐11C]L‐3,4‐dihydroxyphenylalanine (L‐[β‐11C]DOPA, DA precursor ligand), [11C]‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([11C]β‐CFT, DA transporter ligand) and [11C]raclopride (D2 receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of L‐[β‐11C]DOPA (M‐1:41%, M‐2:61%) and [11C]β‐CFT (M‐1:31%, M‐2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M‐2 induced reduced [11C]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell‐based therapies against PD. Synapse 63: 541‐548, 2009. © 2009 Wiley‐Liss, Inc.</abstract><note type="funding">Ministry of Health, Labor and Welfare of Japan</note><note type="funding">Ministry of Education, Culture, Sports, Science and Technology of Japan (Special Coordination Funds)</note><note type="funding">Japan Society for the Promotion of Science (Grant‐in‐Aid for Creative Scientific Research)</note><note type="funding">CREST</note><note type="funding">Japan Science and Technology Agency (JST)</note><subject lang="en"><genre>Keywords</genre><topic>ES cell</topic><topic>PET</topic><topic>monkey</topic><topic>MPTP</topic></subject><relatedItem type="host"><titleInfo><title>Synapse</title></titleInfo><titleInfo type="abbreviated"><title>Synapse</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0887-4476</identifier><identifier type="eISSN">1098-2396</identifier><identifier type="DOI">10.1002/(ISSN)1098-2396</identifier><identifier type="PublisherID">SYN</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>63</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>541</start><end>548</end><total>8</total></extent></part></relatedItem><identifier type="istex">493F050D7EAA94FFA13E53E2530CA3D2352717FA</identifier><identifier type="DOI">10.1002/syn.20634</identifier><identifier type="ArticleID">SYN20634</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2009 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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