Cultured human foetal cerebral cortex, transfected with tyrosine hydroxylase cDNA, as a source of neural transplant material.
Obtaining an adequate supply of foetal dopaminergic tissue to treat Parkinson's disease by neural transplantation can be difficult. In this study primary cultures of human foetal cerebral cortex cells were transfected, using cationic lipids, with a eukaryotic expression vector (pCIneo-THI) containing the cDNA for human tyrosine hydroxylase isoform I (TH). Cortical cells from human (10-14 week) foetuses were cultured for 11 days in vitro and transfected twice with pCIneo-THI during this time. The double transfection process resulted in 3-4% of the cells becoming TH positive. When grafted into the striatum of 6-OHDA lesioned rats the transfected foetal cerebral cortex cells reduced amphetamine-induced circling behaviour by 75%, while grafts of untransfected cells had no significant effect on turning. TH transfected foetal cerebral cortex cells may therefore be a useful alternative supply of tissue for use in neural transplants to treat Parkinson's disease.
Hurley
M J
MJ
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Gerard
D J
DJ
Jauniaux
E
E
Stern
G M
GM
Uchida
K
K
Bradford
H F
HF
D018663:Adrenergic Agents; D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology / Q000637:transplantation*; D003342:Corpus Striatum / Q000201:enzymology / Q000637:transplantation; D018076:DNA, Complementary / Q000627:therapeutic use*; D016332:Fetal Tissue Transplantation / Q000379:methods*; D005333:Fetus; D006801:Humans; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000235:genetics / Q000601:surgery; D014162:Transfection / Q000379:methods*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000627:therapeutic use
D018663:Adrenergic Agents; D018076:DNA, Complementary; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase