Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease
Identifieur interne : 001346 ( Main/Exploration ); précédent : 001345; suivant : 001347Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease
Auteurs : Seung U. Kim [Corée du Sud, Canada] ; In H. Park [Corée du Sud] ; Tae H. Kim [Corée du Sud] ; Kwang S. Kim [Corée du Sud] ; Hyun B. Choi [Canada] ; Seok H. Hong [Corée du Sud] ; Jung H. Bang [Corée du Sud] ; Myung A. Lee [Corée du Sud] ; In S. Joo [Corée du Sud] ; Chong S. Lee [Canada] ; Yong S. Kim [Corée du Sud]Source :
- Neuropathology [ 0919-6544 ] ; 2006-04.
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Abstract
Parkinson disease is a neurodegenerative disease characterized by loss of midbrain dopaminergic neurons resulting in movement disorder. Neural stem cells (NSC) of the CNS have recently aroused a great deal of interest, not only because of their importance in basic research of neural development, but also for their therapeutic potential in neurological disorders. We have recently generated an immortalized human NSC cell line, HB1.F3, via retrovirus‐mediated v‐myc transfer. This line is capable of self‐renewal, is multipotent, and expresses cell specific markers for NSC, ATP‐binding cassettes transporter (ABCG2) and nestin. Next, we co‐transduced the F3 NSC line with genes encoding tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GTPCH1) in order to generate dopamine‐producing NSC. The F3.TH.GTPCH human NSC line expresses TH and GTPCH phenotypes as determined by RT‐PCR, western blotting and immunocytochemistry, and shows a 800 to 2000‐fold increase in production of l‐dihydroxyphenyl alanine in HPLC analysis. A marked improvement in amphetamine‐induced turning behavior was observed in parkinsonian rats implanted with F3.TH.GTPCH cells, but not in control rats receiving F3 NSC. In the animals showing functional improvement, a large number of TH‐positive F3.TH.GTPCH NSC were found at injection sites. These results indicate that human NSC, genetically transduced with TH and GTPCH1 genes, have great potential in clinical utility for cell replacement therapy in patients suffering from Parkinson disease.
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DOI: 10.1111/j.1440-1789.2006.00688.x
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Neural stem cells (NSC) of the CNS have recently aroused a great deal of interest, not only because of their importance in basic research of neural development, but also for their therapeutic potential in neurological disorders. We have recently generated an immortalized human NSC cell line, HB1.F3, via retrovirus‐mediated v‐myc transfer. This line is capable of self‐renewal, is multipotent, and expresses cell specific markers for NSC, ATP‐binding cassettes transporter (ABCG2) and nestin. Next, we co‐transduced the F3 NSC line with genes encoding tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GTPCH1) in order to generate dopamine‐producing NSC. The F3.TH.GTPCH human NSC line expresses TH and GTPCH phenotypes as determined by RT‐PCR, western blotting and immunocytochemistry, and shows a 800 to 2000‐fold increase in production of l‐dihydroxyphenyl alanine in HPLC analysis. A marked improvement in amphetamine‐induced turning behavior was observed in parkinsonian rats implanted with F3.TH.GTPCH cells, but not in control rats receiving F3 NSC. In the animals showing functional improvement, a large number of TH‐positive F3.TH.GTPCH NSC were found at injection sites. These results indicate that human NSC, genetically transduced with TH and GTPCH1 genes, have great potential in clinical utility for cell replacement therapy in patients suffering from Parkinson disease.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Corée du Sud</li></country><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></noRegion><name sortKey="Bang, Jung H" sort="Bang, Jung H" uniqKey="Bang J" first="Jung H." last="Bang">Jung H. Bang</name><name sortKey="Hong, Seok H" sort="Hong, Seok H" uniqKey="Hong S" first="Seok H." last="Hong">Seok H. Hong</name><name sortKey="Joo, In S" sort="Joo, In S" uniqKey="Joo I" first="In S." last="Joo">In S. Joo</name><name sortKey="Kim, Kwang S" sort="Kim, Kwang S" uniqKey="Kim K" first="Kwang S." last="Kim">Kwang S. Kim</name><name sortKey="Kim, Tae H" sort="Kim, Tae H" uniqKey="Kim T" first="Tae H." last="Kim">Tae H. Kim</name><name sortKey="Kim, Yong S" sort="Kim, Yong S" uniqKey="Kim Y" first="Yong S." last="Kim">Yong S. Kim</name><name sortKey="Lee, Myung A" sort="Lee, Myung A" uniqKey="Lee M" first="Myung A." last="Lee">Myung A. Lee</name><name sortKey="Park, In H" sort="Park, In H" uniqKey="Park I" first="In H." last="Park">In H. Park</name></country><country name="Canada"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></noRegion><name sortKey="Choi, Hyun B" sort="Choi, Hyun B" uniqKey="Choi H" first="Hyun B." last="Choi">Hyun B. Choi</name><name sortKey="Lee, Chong S" sort="Lee, Chong S" uniqKey="Lee C" first="Chong S." last="Lee">Chong S. Lee</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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