Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons
Identifieur interne : 000080 ( Main/Exploration ); précédent : 000079; suivant : 000081Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons
Auteurs : Christoph Proschel [États-Unis] ; Jennifer. Stripay [États-Unis] ; Chung Shih [États-Unis] ; Joshua. Munger [États-Unis] ; Mark. Noble [États-Unis]Source :
- EMBO Molecular Medicine [ 1757-4676 ] ; 2014.
Abstract
In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically-relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDAsBMP, that are generated
Url:
DOI: 10.1002/emmm.201302878
PubMed: 24477866
PubMed Central: 3992077
Affiliations:
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Stripay</name><affiliation wicri:level="2"><nlm:aff id="au1"><institution>Department for Biomedical Genetics, University of Rochester</institution><addr-line>Rochester, NY, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="au3"><institution>Neuroscience Graduate Program, University of Rochester</institution><addr-line>Rochester, NY, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Shih, Chung Hsuan" sort="Shih, Chung Hsuan" uniqKey="Shih C" first="Chung" last="Shih">Chung Shih</name><affiliation wicri:level="2"><nlm:aff id="au1"><institution>Department for Biomedical Genetics, University of Rochester</institution><addr-line>Rochester, NY, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="au4"><institution>Department of Pathology, University of Rochester</institution><addr-line>Rochester, NY, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Munger, Joshua C" sort="Munger, Joshua C" uniqKey="Munger J" first="Joshua" last="Munger">Joshua. Munger</name><affiliation wicri:level="2"><nlm:aff id="au5"><institution>Department of Biochemistry and Biophysics, University of Rochester</institution><addr-line>Rochester, NY, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Noble, Mark D" sort="Noble, Mark D" uniqKey="Noble M" first="Mark" last="Noble">Mark. Noble</name><affiliation wicri:level="2"><nlm:aff id="au1"><institution>Department for Biomedical Genetics, University of Rochester</institution><addr-line>Rochester, NY, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="au2"><institution>Stem Cell and Regenerative Medicine Institute, University of Rochester</institution><addr-line>Rochester, NY, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">EMBO Molecular Medicine</title><idno type="ISSN">1757-4676</idno><idno type="e-ISSN">1757-4684</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically-relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDAs<sup>BMP</sup>, that are generated <italic>in vitro</italic> by directed differentiation of glial precursors. GDAs<sup>BMP</sup> produce multiple agents of interest as treatments for PD and other neurodegenerative disorders, including BDNF, GDNF, neurturin and IGF1. GDAs<sup>BMP</sup> also exhibit increased levels of antioxidant pathway components, including levels of NADPH and glutathione. Delayed GDA<sup>BMP</sup> transplantation into the 6-hydroxydopamine lesioned rat striatum restored tyrosine hydroxylase expression and promoted behavioral recovery. GDA<sup>BMP</sup> transplantation also rescued pathological changes not prevented in other studies, such as the rescue of parvalbumin<sup>+</sup> GABAergic interneurons. Consistent with expression of the synaptic modulatory proteins thrombospondin-1 and 2 by GDAs<sup>BMP</sup>, increased expression of the synaptic protein synaptophysin was also observed. Thus, GDAs<sup>BMP</sup> offer a multimodal support cell therapy that provides multiple benefits without requiring prior genetic manipulation.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Allen, Sj" uniqKey="Allen S">SJ Allen</name></author><author><name sortKey="Watson, Jj" uniqKey="Watson J">JJ Watson</name></author><author><name sortKey="Shoemark, Dk" uniqKey="Shoemark D">DK Shoemark</name></author><author><name sortKey="Barua, Nu" uniqKey="Barua N">NU Barua</name></author><author><name sortKey="Patel, Nk" uniqKey="Patel N">NK Patel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Altar, Ca" uniqKey="Altar C">CA Altar</name></author><author><name sortKey="Boylan, Cb" uniqKey="Boylan C">CB Boylan</name></author><author><name sortKey="Jackson, C" uniqKey="Jackson C">C Jackson</name></author><author><name sortKey="Hershenson, S" uniqKey="Hershenson S">S Hershenson</name></author><author><name 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Przedborski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zuch, Cl" uniqKey="Zuch C">CL Zuch</name></author><author><name sortKey="David, D" uniqKey="David D">D David</name></author><author><name sortKey="Ujhelyi, L" uniqKey="Ujhelyi L">L Ujhelyi</name></author><author><name sortKey="Hudson, Jl" uniqKey="Hudson J">JL Hudson</name></author><author><name sortKey="Gerhardt, Ga" uniqKey="Gerhardt G">GA Gerhardt</name></author><author><name sortKey="Kaplan, Pl" uniqKey="Kaplan P">PL Kaplan</name></author><author><name sortKey="Bickford, Pc" uniqKey="Bickford P">PC Bickford</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Proschel, Christoph" sort="Proschel, Christoph" uniqKey="Proschel C" first="Christoph" last="Proschel">Christoph Proschel</name></region><name sortKey="Munger, Joshua C" sort="Munger, Joshua C" uniqKey="Munger J" first="Joshua" last="Munger">Joshua. Munger</name><name sortKey="Noble, Mark D" sort="Noble, Mark D" uniqKey="Noble M" first="Mark" last="Noble">Mark. Noble</name><name sortKey="Noble, Mark D" sort="Noble, Mark D" uniqKey="Noble M" first="Mark" last="Noble">Mark. Noble</name><name sortKey="Proschel, Christoph" sort="Proschel, Christoph" uniqKey="Proschel C" first="Christoph" last="Proschel">Christoph Proschel</name><name sortKey="Shih, Chung Hsuan" sort="Shih, Chung Hsuan" uniqKey="Shih C" first="Chung" last="Shih">Chung Shih</name><name sortKey="Shih, Chung Hsuan" sort="Shih, Chung Hsuan" uniqKey="Shih C" first="Chung" last="Shih">Chung Shih</name><name sortKey="Stripay, Jennifer L" sort="Stripay, Jennifer L" uniqKey="Stripay J" first="Jennifer" last="Stripay">Jennifer. Stripay</name><name sortKey="Stripay, Jennifer L" sort="Stripay, Jennifer L" uniqKey="Stripay J" first="Jennifer" last="Stripay">Jennifer. Stripay</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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