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 : 000A22 ( Main/Exploration ); précédent : 000A21; suivant : 000A23Multitracer 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 [Japon] ; Tsuyoshi Okuno [Japon] ; Yutaka Suzuki [Japon] ; Takashi Nakayama [Japon] ; Takeharu Kakiuchi [Japon] ; Naomi Takino [Japon] ; Asako Iida [Japon] ; Fumiko Ono [Japon] ; Keiji Terao [Japon] ; Nobuo Inoue [Japon] ; Imaharu Nakano [Japon] ; Yasushi Kondo [Japon] ; Hideo Tsukada [Japon]Source :
- 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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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><affiliations><list><country><li>Japon</li></country><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><noRegion><name sortKey="Muramatsu, Shin Chi" sort="Muramatsu, Shin Chi" uniqKey="Muramatsu S" first="Shin-Ichi" last="Muramatsu">Shin-Ichi Muramatsu</name></noRegion><name sortKey="Iida, Asako" sort="Iida, Asako" uniqKey="Iida A" first="Asako" last="Iida">Asako Iida</name><name sortKey="Inoue, Nobuo" sort="Inoue, Nobuo" uniqKey="Inoue N" first="Nobuo" last="Inoue">Nobuo Inoue</name><name sortKey="Kakiuchi, Takeharu" sort="Kakiuchi, Takeharu" uniqKey="Kakiuchi T" first="Takeharu" last="Kakiuchi">Takeharu Kakiuchi</name><name sortKey="Kondo, Yasushi" sort="Kondo, Yasushi" uniqKey="Kondo Y" first="Yasushi" last="Kondo">Yasushi Kondo</name><name sortKey="Nakano, Imaharu" sort="Nakano, Imaharu" uniqKey="Nakano I" first="Imaharu" last="Nakano">Imaharu Nakano</name><name sortKey="Nakayama, Takashi" sort="Nakayama, Takashi" uniqKey="Nakayama T" first="Takashi" last="Nakayama">Takashi Nakayama</name><name sortKey="Okuno, Tsuyoshi" sort="Okuno, Tsuyoshi" uniqKey="Okuno T" first="Tsuyoshi" last="Okuno">Tsuyoshi Okuno</name><name sortKey="Ono, Fumiko" sort="Ono, Fumiko" uniqKey="Ono F" first="Fumiko" last="Ono">Fumiko Ono</name><name sortKey="Suzuki, Yutaka" sort="Suzuki, Yutaka" uniqKey="Suzuki Y" first="Yutaka" last="Suzuki">Yutaka Suzuki</name><name sortKey="Takino, Naomi" sort="Takino, Naomi" uniqKey="Takino N" first="Naomi" last="Takino">Naomi Takino</name><name sortKey="Terao, Keiji" sort="Terao, Keiji" uniqKey="Terao K" first="Keiji" last="Terao">Keiji Terao</name><name sortKey="Tsukada, Hideo" sort="Tsukada, Hideo" uniqKey="Tsukada H" first="Hideo" last="Tsukada">Hideo Tsukada</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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