Expression of a novel gene product by transplants of genetically modified primary fibroblasts in the central nervous system
Identifieur interne : 000F88 ( Istex/Corpus ); précédent : 000F87; suivant : 000F89Expression of a novel gene product by transplants of genetically modified primary fibroblasts in the central nervous system
Auteurs : D. B Doering ; P. L. ChangSource :
- Journal of Neuroscience Research [ 0360-4012 ] ; 1991-07.
English descriptors
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Abstract
Primary fibroblasts initiated from skin biopsies of Wistar rats were transfected with a plasmid that encodes the human growth hormone and the neomycin resistance genes. Cell clones selected for G418 resistance and expressing high levels of human growth hormone were propagated in vitro and subsequently transplanted into the cerebral cortex of adult allogeneic rats. Grafts were examined by immunocytochemistry at weekly intervals up to 2 months. Fibroblasts in the transplants survived and expressed growth hormone clearly up to 4 weeks, but showed reduced expression at 6 to 8 weeks. Significant levels of human growth hormone were also detected by radioimmunoassay in the serum of the host rats up to 1 month. The experiments demonstrate that primary fibroblasts can be genetically modified to deliver a new gene product into the central nervous system, and the gene product can pass the blood‐brain barrier to enter the systemic circulation. This model illustrates the potential to introduce desired products into the brain through the genetic alteration of autologous primary fibroblasts.
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DOI: 10.1002/jnr.490290304
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B" last="Doering">D. B Doering</name><affiliation><mods:affiliation>Department of Biomedical Sciences(Anatomy), McMaster University, Hamilton, Ontario, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Anatomy, HSC 1R1, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5</mods:affiliation></affiliation></author><author><name sortKey="Chang, P L" sort="Chang, P L" uniqKey="Chang P" first="P. L." last="Chang">P. L. Chang</name><affiliation><mods:affiliation>Department of Biomedical Sciences(Anatomy), McMaster University, Hamilton, Ontario, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Neuroscience Research</title><title level="j" type="abbrev">J. Neurosci. 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L.</namePart><namePart type="family">Chang</namePart><affiliation>Department of Biomedical Sciences(Anatomy), McMaster University, Hamilton, Ontario, Canada</affiliation><affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">1991-07</dateIssued><dateCaptured encoding="w3cdtf">1990-09-26</dateCaptured><dateValid encoding="w3cdtf">1990-11-30</dateValid><copyrightDate encoding="w3cdtf">1991</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="tables">1</extent><extent unit="references">31</extent></physicalDescription><abstract lang="en">Primary fibroblasts initiated from skin biopsies of Wistar rats were transfected with a plasmid that encodes the human growth hormone and the neomycin resistance genes. Cell clones selected for G418 resistance and expressing high levels of human growth hormone were propagated in vitro and subsequently transplanted into the cerebral cortex of adult allogeneic rats. Grafts were examined by immunocytochemistry at weekly intervals up to 2 months. Fibroblasts in the transplants survived and expressed growth hormone clearly up to 4 weeks, but showed reduced expression at 6 to 8 weeks. Significant levels of human growth hormone were also detected by radioimmunoassay in the serum of the host rats up to 1 month. The experiments demonstrate that primary fibroblasts can be genetically modified to deliver a new gene product into the central nervous system, and the gene product can pass the blood‐brain barrier to enter the systemic circulation. This model illustrates the potential to introduce desired products into the brain through the genetic alteration of autologous primary fibroblasts.</abstract><subject lang="en"><genre>keywords</genre><topic>rat</topic><topic>human growth hormone</topic><topic>transfection</topic><topic>immunocytochemistry</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Neuroscience Research</title></titleInfo><titleInfo type="abbreviated"><title>J. Neurosci. 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