ParkinsonCanadaV1, PascalFrancis, Checkpoint, bibRecord, 000966

Complications of a trophic xenotransplant approach in parkinsonian monkeys

Identifieur interne : 000966 ( PascalFrancis/Checkpoint ); précédent : 000965; suivant : 000967

Complications of a trophic xenotransplant approach in parkinsonian monkeys

Auteurs : Pierre J. Blanchet [États-Unis, Canada] ; Spiros Konitsiotis [États-Unis, Grèce] ; Hideki Mochizuki [États-Unis, Japon] ; Ryszard Pluta [États-Unis] ; Dwaine F. Emerich [États-Unis] ; Thomas N. Chase [États-Unis] ; M. Maral Mouradian [États-Unis]

Source :

Progress in neuro-psychopharmacology & biological psychiatry [ 0278-5846 ] ; 2003.

RBID : Pascal:03-0390767

Descripteurs français

Pascal (Inist)
- Parkinson maladie, Facteur GDNF, Transplantation, Cellule, Encapsulation, Thérapie génique, Chimiothérapie, Traitement, Implant, Efficacité traitement, Complication, Toxicité, Animal, Singe, Corps strié, Activité biologique, Encéphale, Système nerveux central, Long terme, Lignée BHK.
Wicri :
- topic : Singe.

English descriptors

KwdEn :
- Animal, Biological activity, Brain (vertebrata), Cell, Central nervous system, Chemotherapy, Complication, Corpus striatum, Encapsulation, Gene therapy, Glial cell line derived neurotrophic factor, Implant, Long term, Monkey, Parkinson disease, Toxicity, Transplantation, Treatment, Treatment efficiency.

Abstract

Various restorative cell transplantation strategies have been investigated to substitute for lost dopamine (DA) neurons or to enhance DA synthesis in Parkinson's disease. Intracerebral implantation of engineered cells encapsulated in a semipermeable polymer membrane constitutes one way to deliver bioactive substances unable to cross the blood-brain barrier while avoiding the need for long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF) has shown trophic effects on DA neurons but effective and sustained delivery within the brain parenchyma remains problematic. The long-term efficacy and late complications of a xenotransplant approach utilizing GDNF-expressing encapsulated baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned parkinsonian cynomolgus monkeys received five devices containing active or inert cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart and animals were sacrificed 4 months later for analyses. No definite motor benefit was observed, DA levels were comparable between GDNF- and control cell-implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis in the explanted devices were negligible. The brain tissue surrounding all implants showed an intense immune reaction with prominent "foreign body" inflammatory infiltrates. Membrane biophysics, the cell type used, and the extended period of time the devices remained in situ may have contributed to the negative outcome and should be addressed in future investigations using this approach.

Affiliations:

Canada, Grèce, Japon, États-Unis
Tokyo

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Le document en format XML

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<front><div type="abstract" xml:lang="en">Various restorative cell transplantation strategies have been investigated to substitute for lost dopamine (DA) neurons or to enhance DA synthesis in Parkinson's disease. Intracerebral implantation of engineered cells encapsulated in a semipermeable polymer membrane constitutes one way to deliver bioactive substances unable to cross the blood-brain barrier while avoiding the need for long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF) has shown trophic effects on DA neurons but effective and sustained delivery within the brain parenchyma remains problematic. The long-term efficacy and late complications of a xenotransplant approach utilizing GDNF-expressing encapsulated baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned parkinsonian cynomolgus monkeys received five devices containing active or inert cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart and animals were sacrificed 4 months later for analyses. No definite motor benefit was observed, DA levels were comparable between GDNF- and control cell-implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis in the explanted devices were negligible. The brain tissue surrounding all implants showed an intense immune reaction with prominent "foreign body" inflammatory infiltrates. Membrane biophysics, the cell type used, and the extended period of time the devices remained in situ may have contributed to the negative outcome and should be addressed in future investigations using this approach.</div>
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<fC01 i1="01" l="ENG"><s0>Various restorative cell transplantation strategies have been investigated to substitute for lost dopamine (DA) neurons or to enhance DA synthesis in Parkinson's disease. Intracerebral implantation of engineered cells encapsulated in a semipermeable polymer membrane constitutes one way to deliver bioactive substances unable to cross the blood-brain barrier while avoiding the need for long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF) has shown trophic effects on DA neurons but effective and sustained delivery within the brain parenchyma remains problematic. The long-term efficacy and late complications of a xenotransplant approach utilizing GDNF-expressing encapsulated baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned parkinsonian cynomolgus monkeys received five devices containing active or inert cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart and animals were sacrificed 4 months later for analyses. No definite motor benefit was observed, DA levels were comparable between GDNF- and control cell-implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis in the explanted devices were negligible. The brain tissue surrounding all implants showed an intense immune reaction with prominent "foreign body" inflammatory infiltrates. Membrane biophysics, the cell type used, and the extended period of time the devices remained in situ may have contributed to the negative outcome and should be addressed in future investigations using this approach.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02B06</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Parkinson maladie</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Parkinson disease</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Parkinson enfermedad</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Facteur GDNF</s0>
<s5>04</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Glial cell line derived neurotrophic factor</s0>
<s5>04</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Factor GDNF</s0>
<s5>04</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Transplantation</s0>
<s5>07</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Transplantation</s0>
<s5>07</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Trasplantación</s0>
<s5>07</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Cellule</s0>
<s5>10</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Cell</s0>
<s5>10</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Célula</s0>
<s5>10</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Encapsulation</s0>
<s5>11</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Encapsulation</s0>
<s5>11</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Encapsulación</s0>
<s5>11</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Thérapie génique</s0>
<s5>12</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Gene therapy</s0>
<s5>12</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Terapia génica</s0>
<s5>12</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Chimiothérapie</s0>
<s5>13</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Chemotherapy</s0>
<s5>13</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Quimioterapia</s0>
<s5>13</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Traitement</s0>
<s5>14</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Treatment</s0>
<s5>14</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Tratamiento</s0>
<s5>14</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Implant</s0>
<s5>15</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Implant</s0>
<s5>15</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Implante</s0>
<s5>15</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Efficacité traitement</s0>
<s5>16</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Treatment efficiency</s0>
<s5>16</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Eficacia tratamiento</s0>
<s5>16</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Complication</s0>
<s5>17</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Complication</s0>
<s5>17</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Complicación</s0>
<s5>17</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Toxicité</s0>
<s5>18</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Toxicity</s0>
<s5>18</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Toxicidad</s0>
<s5>18</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Animal</s0>
<s5>19</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG"><s0>Animal</s0>
<s5>19</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA"><s0>Animal</s0>
<s5>19</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE"><s0>Singe</s0>
<s5>20</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG"><s0>Monkey</s0>
<s5>20</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA"><s0>Mono</s0>
<s5>20</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE"><s0>Corps strié</s0>
<s5>21</s5>
</fC03>
<fC03 i1="15" i2="X" l="ENG"><s0>Corpus striatum</s0>
<s5>21</s5>
</fC03>
<fC03 i1="15" i2="X" l="SPA"><s0>Cuerpo estriado</s0>
<s5>21</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE"><s0>Activité biologique</s0>
<s5>22</s5>
</fC03>
<fC03 i1="16" i2="X" l="ENG"><s0>Biological activity</s0>
<s5>22</s5>
</fC03>
<fC03 i1="16" i2="X" l="SPA"><s0>Actividad biológica</s0>
<s5>22</s5>
</fC03>
<fC03 i1="17" i2="X" l="FRE"><s0>Encéphale</s0>
<s5>33</s5>
</fC03>
<fC03 i1="17" i2="X" l="ENG"><s0>Brain (vertebrata)</s0>
<s5>33</s5>
</fC03>
<fC03 i1="17" i2="X" l="SPA"><s0>Encéfalo</s0>
<s5>33</s5>
</fC03>
<fC03 i1="18" i2="X" l="FRE"><s0>Système nerveux central</s0>
<s5>34</s5>
</fC03>
<fC03 i1="18" i2="X" l="ENG"><s0>Central nervous system</s0>
<s5>34</s5>
</fC03>
<fC03 i1="18" i2="X" l="SPA"><s0>Sistema nervioso central</s0>
<s5>34</s5>
</fC03>
<fC03 i1="19" i2="X" l="FRE"><s0>Long terme</s0>
<s5>78</s5>
</fC03>
<fC03 i1="19" i2="X" l="ENG"><s0>Long term</s0>
<s5>78</s5>
</fC03>
<fC03 i1="19" i2="X" l="SPA"><s0>Largo plazo</s0>
<s5>78</s5>
</fC03>
<fC03 i1="20" i2="X" l="FRE"><s0>Lignée BHK</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Primates</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Primates</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Primates</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Système nerveux pathologie</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Nervous system diseases</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervioso patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0>
<s5>38</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Encéphale pathologie</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Cerebral disorder</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Encéfalo patología</s0>
<s5>39</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Maladie dégénérative</s0>
<s5>41</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Degenerative disease</s0>
<s5>41</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Chirurgie</s0>
<s5>53</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Surgery</s0>
<s5>53</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Cirugía</s0>
<s5>53</s5>
</fC07>
<fN21><s1>272</s1>
</fN21>
<fN82><s1>PSI</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations><list><country><li>Canada</li>
<li>Grèce</li>
<li>Japon</li>
<li>États-Unis</li>
</country>
<settlement><li>Tokyo</li>
</settlement>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name>
</noRegion>
<name sortKey="Chase, Thomas N" sort="Chase, Thomas N" uniqKey="Chase T" first="Thomas N." last="Chase">Thomas N. Chase</name>
<name sortKey="Emerich, Dwaine F" sort="Emerich, Dwaine F" uniqKey="Emerich D" first="Dwaine F." last="Emerich">Dwaine F. Emerich</name>
<name sortKey="Emerich, Dwaine F" sort="Emerich, Dwaine F" uniqKey="Emerich D" first="Dwaine F." last="Emerich">Dwaine F. Emerich</name>
<name sortKey="Konitsiotis, Spiros" sort="Konitsiotis, Spiros" uniqKey="Konitsiotis S" first="Spiros" last="Konitsiotis">Spiros Konitsiotis</name>
<name sortKey="Mochizuki, Hideki" sort="Mochizuki, Hideki" uniqKey="Mochizuki H" first="Hideki" last="Mochizuki">Hideki Mochizuki</name>
<name sortKey="Mouradian, M Maral" sort="Mouradian, M Maral" uniqKey="Mouradian M" first="M. Maral" last="Mouradian">M. Maral Mouradian</name>
<name sortKey="Pluta, Ryszard" sort="Pluta, Ryszard" uniqKey="Pluta R" first="Ryszard" last="Pluta">Ryszard Pluta</name>
</country>
<country name="Canada"><noRegion><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name>
</noRegion>
</country>
<country name="Grèce"><noRegion><name sortKey="Konitsiotis, Spiros" sort="Konitsiotis, Spiros" uniqKey="Konitsiotis S" first="Spiros" last="Konitsiotis">Spiros Konitsiotis</name>
</noRegion>
</country>
<country name="Japon"><noRegion><name sortKey="Mochizuki, Hideki" sort="Mochizuki, Hideki" uniqKey="Mochizuki H" first="Hideki" last="Mochizuki">Hideki Mochizuki</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

La maladie de Parkinson au Canada (serveur d'exploration)

Complications of a trophic xenotransplant approach in parkinsonian monkeys

Complications of a trophic xenotransplant approach in parkinsonian monkeys

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