Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of parkinson disease
Identifieur interne : 002693 ( Main/Exploration ); précédent : 002692; suivant : 002694Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of parkinson disease
Auteurs : Joseph Flores [Canada] ; Ivan L. Cepeda [Canada] ; Michael L. Comfeldt [États-Unis] ; John R. O'Kusky [Canada] ; Doris J. Doudet [Canada]Source :
- Journal of neuropathology and experimental neurology [ 0022-3069 ] ; 2007.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Animals, Cell Survival, Cell Transplantation (methods), Characterization, Corpus Striatum (pathology), Corpus Striatum (physiopathology), Corpus Striatum (surgery), Disease Models, Animal, Epithelial cell, Gelatin (therapeutic use), Human, Humans, Immunohistochemistry, Implant, Long term, Male, Microscopy, Electron, Transmission (methods), Microspheres, Models, Nerve Tissue Proteins (metabolism), Nervous system diseases, Parkinson Disease (etiology), Parkinson Disease (physiopathology), Parkinson Disease (surgery), Parkinson disease, Pigment Epithelium of Eye (physiology), Pigment Epithelium of Eye (transplantation), Pigment Epithelium of Eye (ultrastructure), Pigment cell, Rats, Rats, Sprague-Dawley, Retina, Survival, Time Factors, Transplantation, Transplantation, Heterologous (methods).
- MESH :
- chemical , metabolism : Nerve Tissue Proteins.
- chemical , therapeutic use : Gelatin.
- etiology : Parkinson Disease.
- methods : Cell Transplantation, Microscopy, Electron, Transmission, Transplantation, Heterologous.
- pathology : Corpus Striatum.
- physiology : Pigment Epithelium of Eye.
- physiopathology : Corpus Striatum, Parkinson Disease.
- surgery : Corpus Striatum, Parkinson Disease.
- transplantation : Pigment Epithelium of Eye.
- ultrastructure : Pigment Epithelium of Eye.
- Animals, Cell Survival, Disease Models, Animal, Humans, Male, Microspheres, Rats, Rats, Sprague-Dawley, Time Factors.
Abstract
Previous studies have demonstrated that the intrastriatal implantation of human retinal pigment epithelial cells attached to gelatin microcarriers (hRPE-GM) ameliorates behavioral deficits in animal models of Parkinson disease. However, there are only sparse data on cell survival in the host. In this study, we characterized a variety of retinal pigment epithelial (RPE)-specific markers in vitro and used these markers to investigate the long-term survival of hRPE-GM implants. Sprague-Dawley rats (n = 22) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and implanted with hRPE-GM without immunosuppression. Rats were euthanized at 48 hours, 7 days, 4 weeks, and 5 months postimplant and immunohistochemically processed using the following antibodies: 1) human-specific nuclear mitotic apparatus protein (NuMA-Ab2), 2) epithelial-specific extracellular matrix metalloproteinase inducer (EMM-PRIN), 3) RPE cell-specific RPE65, and the inflammation markers 4) glial fibrillary acidic protein and 5) ED1 (rat CD68). Our analysis revealed NuMA-, EMMPRIN-, and RPE65-immunoreactive cells at different times postimplant. The morphologic features of hRPE cell implants (at 48 hours and 5 months) were confirmed by electron microscopy. Furthermore, despite evidence of chronic inflammation at the later time point, there is an appreciable number of surviving hRPE cells. This study suggests that hRPE-GM implants can survive in the absence of immunosuppression and can be potentially used as an alternative for treating Parkinson disease.
Affiliations:
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Cell Survival</term>
<term>Cell Transplantation (methods)</term>
<term>Characterization</term>
<term>Corpus Striatum (pathology)</term>
<term>Corpus Striatum (physiopathology)</term>
<term>Corpus Striatum (surgery)</term>
<term>Disease Models, Animal</term>
<term>Epithelial cell</term>
<term>Gelatin (therapeutic use)</term>
<term>Human</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>Implant</term>
<term>Long term</term>
<term>Male</term>
<term>Microscopy, Electron, Transmission (methods)</term>
<term>Microspheres</term>
<term>Models</term>
<term>Nerve Tissue Proteins (metabolism)</term>
<term>Nervous system diseases</term>
<term>Parkinson Disease (etiology)</term>
<term>Parkinson Disease (physiopathology)</term>
<term>Parkinson Disease (surgery)</term>
<term>Parkinson disease</term>
<term>Pigment Epithelium of Eye (physiology)</term>
<term>Pigment Epithelium of Eye (transplantation)</term>
<term>Pigment Epithelium of Eye (ultrastructure)</term>
<term>Pigment cell</term>
<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
<term>Retina</term>
<term>Survival</term>
<term>Time Factors</term>
<term>Transplantation</term>
<term>Transplantation, Heterologous (methods)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nerve Tissue Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Gelatin</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Cell Transplantation</term>
<term>Microscopy, Electron, Transmission</term>
<term>Transplantation, Heterologous</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Pigment Epithelium of Eye</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Corpus Striatum</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Corpus Striatum</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>Pigment Epithelium of Eye</term>
</keywords>
<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Pigment Epithelium of Eye</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Survival</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Male</term>
<term>Microspheres</term>
<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
<term>Time Factors</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term>
<term>Parkinson maladie</term>
<term>Caractérisation</term>
<term>Survie</term>
<term>Long terme</term>
<term>Implant</term>
<term>Homme</term>
<term>Rétine</term>
<term>Cellule pigmentaire</term>
<term>Cellule épithéliale</term>
<term>Modèle</term>
<term>Immunohistochimie</term>
<term>Transplantation</term>
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<front><div type="abstract" xml:lang="en">Previous studies have demonstrated that the intrastriatal implantation of human retinal pigment epithelial cells attached to gelatin microcarriers (hRPE-GM) ameliorates behavioral deficits in animal models of Parkinson disease. However, there are only sparse data on cell survival in the host. In this study, we characterized a variety of retinal pigment epithelial (RPE)-specific markers in vitro and used these markers to investigate the long-term survival of hRPE-GM implants. Sprague-Dawley rats (n = 22) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and implanted with hRPE-GM without immunosuppression. Rats were euthanized at 48 hours, 7 days, 4 weeks, and 5 months postimplant and immunohistochemically processed using the following antibodies: 1) human-specific nuclear mitotic apparatus protein (NuMA-Ab2), 2) epithelial-specific extracellular matrix metalloproteinase inducer (EMM-PRIN), 3) RPE cell-specific RPE65, and the inflammation markers 4) glial fibrillary acidic protein and 5) ED1 (rat CD68). Our analysis revealed NuMA-, EMMPRIN-, and RPE65-immunoreactive cells at different times postimplant. The morphologic features of hRPE cell implants (at 48 hours and 5 months) were confirmed by electron microscopy. Furthermore, despite evidence of chronic inflammation at the later time point, there is an appreciable number of surviving hRPE cells. This study suggests that hRPE-GM implants can survive in the absence of immunosuppression and can be potentially used as an alternative for treating Parkinson disease.</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>États-Unis</li>
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<region><li>New Jersey</li>
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<tree><country name="Canada"><noRegion><name sortKey="Flores, Joseph" sort="Flores, Joseph" uniqKey="Flores J" first="Joseph" last="Flores">Joseph Flores</name>
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<name sortKey="Cepeda, Ivan L" sort="Cepeda, Ivan L" uniqKey="Cepeda I" first="Ivan L." last="Cepeda">Ivan L. Cepeda</name>
<name sortKey="Doudet, Doris J" sort="Doudet, Doris J" uniqKey="Doudet D" first="Doris J." last="Doudet">Doris J. Doudet</name>
<name sortKey="O Kusky, John R" sort="O Kusky, John R" uniqKey="O Kusky J" first="John R." last="O'Kusky">John R. O'Kusky</name>
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<country name="États-Unis"><region name="New Jersey"><name sortKey="Comfeldt, Michael L" sort="Comfeldt, Michael L" uniqKey="Comfeldt M" first="Michael L." last="Comfeldt">Michael L. Comfeldt</name>
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