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 : 001059 ( PubMed/Corpus ); précédent : 001058; suivant : 001060Characterization 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 ; Ivan L. Cepeda ; Michael L. Cornfeldt ; John R. O'Kusky ; Doris J. DoudetSource :
- Journal of neuropathology and experimental neurology [ 0022-3069 ] ; 2007.
English descriptors
- KwdEn :
- Animals, Cell Survival, Cell Transplantation (methods), Corpus Striatum (pathology), Corpus Striatum (physiopathology), Corpus Striatum (surgery), Disease Models, Animal, Gelatin (therapeutic use), Humans, Male, Microscopy, Electron, Transmission (methods), Microspheres, Nerve Tissue Proteins (metabolism), Parkinson Disease (etiology), Parkinson Disease (physiopathology), Parkinson Disease (surgery), Pigment Epithelium of Eye (physiology), Pigment Epithelium of Eye (transplantation), Pigment Epithelium of Eye (ultrastructure), Rats, Rats, Sprague-Dawley, Time Factors, 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 (EMMPRIN), 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.
DOI: 10.1097/nen.0b013e318093e53a
PubMed: 17620984
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of Parkinson disease.</title><author><name sortKey="Flores, Joseph" sort="Flores, Joseph" uniqKey="Flores J" first="Joseph" last="Flores">Joseph Flores</name><affiliation><nlm:affiliation>Department of Medicine/Neurology and the Pacific Parkinson's Research Centre, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, Canada. joflores@interchange.ubc.ca</nlm:affiliation></affiliation></author><author><name sortKey="Cepeda, Ivan L" sort="Cepeda, Ivan L" uniqKey="Cepeda I" first="Ivan L" last="Cepeda">Ivan L. Cepeda</name></author><author><name sortKey="Cornfeldt, Michael L" sort="Cornfeldt, Michael L" uniqKey="Cornfeldt M" first="Michael L" last="Cornfeldt">Michael L. Cornfeldt</name></author><author><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></author><author><name sortKey="Doudet, Doris J" sort="Doudet, Doris J" uniqKey="Doudet D" first="Doris J" last="Doudet">Doris J. Doudet</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2007">2007</date><idno type="RBID">pubmed:17620984</idno><idno type="pmid">17620984</idno><idno type="doi">10.1097/nen.0b013e318093e53a</idno><idno type="wicri:Area/PubMed/Corpus">001059</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001059</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of Parkinson disease.</title><author><name sortKey="Flores, Joseph" sort="Flores, Joseph" uniqKey="Flores J" first="Joseph" last="Flores">Joseph Flores</name><affiliation><nlm:affiliation>Department of Medicine/Neurology and the Pacific Parkinson's Research Centre, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, Canada. joflores@interchange.ubc.ca</nlm:affiliation></affiliation></author><author><name sortKey="Cepeda, Ivan L" sort="Cepeda, Ivan L" uniqKey="Cepeda I" first="Ivan L" last="Cepeda">Ivan L. Cepeda</name></author><author><name sortKey="Cornfeldt, Michael L" sort="Cornfeldt, Michael L" uniqKey="Cornfeldt M" first="Michael L" last="Cornfeldt">Michael L. Cornfeldt</name></author><author><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></author><author><name sortKey="Doudet, Doris J" sort="Doudet, Doris J" uniqKey="Doudet D" first="Doris J" last="Doudet">Doris J. Doudet</name></author></analytic><series><title level="j">Journal of neuropathology and experimental neurology</title><idno type="ISSN">0022-3069</idno><imprint><date when="2007" type="published">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Survival</term><term>Cell Transplantation (methods)</term><term>Corpus Striatum (pathology)</term><term>Corpus Striatum (physiopathology)</term><term>Corpus Striatum (surgery)</term><term>Disease Models, Animal</term><term>Gelatin (therapeutic use)</term><term>Humans</term><term>Male</term><term>Microscopy, Electron, Transmission (methods)</term><term>Microspheres</term><term>Nerve Tissue Proteins (metabolism)</term><term>Parkinson Disease (etiology)</term><term>Parkinson Disease (physiopathology)</term><term>Parkinson Disease (surgery)</term><term>Pigment Epithelium of Eye (physiology)</term><term>Pigment Epithelium of Eye (transplantation)</term><term>Pigment Epithelium of Eye (ultrastructure)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Time Factors</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></keywords></textClass></profileDesc></teiHeader><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 (EMMPRIN), 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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17620984</PMID><DateCreated><Year>2007</Year><Month>07</Month><Day>10</Day></DateCreated><DateCompleted><Year>2007</Year><Month>08</Month><Day>31</Day></DateCompleted><DateRevised><Year>2007</Year><Month>07</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-3069</ISSN><JournalIssue CitedMedium="Print"><Volume>66</Volume><Issue>7</Issue><PubDate><Year>2007</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Journal of neuropathology and experimental neurology</Title><ISOAbbreviation>J. Neuropathol. Exp. Neurol.</ISOAbbreviation></Journal><ArticleTitle>Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of Parkinson disease.</ArticleTitle><Pagination><MedlinePgn>585-96</MedlinePgn></Pagination><Abstract><AbstractText>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 (EMMPRIN), 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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Flores</LastName><ForeName>Joseph</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Medicine/Neurology and the Pacific Parkinson's Research Centre, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, Canada. joflores@interchange.ubc.ca</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cepeda</LastName><ForeName>Ivan L</ForeName><Initials>IL</Initials></Author><Author ValidYN="Y"><LastName>Cornfeldt</LastName><ForeName>Michael L</ForeName><Initials>ML</Initials></Author><Author ValidYN="Y"><LastName>O'Kusky</LastName><ForeName>John R</ForeName><Initials>JR</Initials></Author><Author ValidYN="Y"><LastName>Doudet</LastName><ForeName>Doris J</ForeName><Initials>DJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Neuropathol Exp Neurol</MedlineTA><NlmUniqueID>2985192R</NlmUniqueID><ISSNLinking>0022-3069</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009419">Nerve Tissue Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>9000-70-8</RegistryNumber><NameOfSubstance UI="D005780">Gelatin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell 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