Genetically modified human embryonic stem cells relieve symptomatic motor behavior in a rat model of Parkinson's disease.
Embryonic stem (ES) cells have great potential as a cell source for cell replacement therapy. To investigate the possibility of using ES cells as a carrier of therapeutic gene(s), human ES cells (MB03) were co-transfected with cDNAs coding for tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GTPCH I), then bulk-selected in the presence of neomycin and hygromycin-B. Successful transfection was confirmed by Western immunoblotting and RT-PCR. The genetically modified ES cells (bk-THGC) were found to produce a significant amount of L-dopa spontaneously and relieved apomorphine-induced asymmetric motor behavior by approximately 54% when grafted into striatum of 6-OHDA-denervated rat brain. The number of rotations, however, increased up to 176+/-18% in 6 weeks when PBS was used instead (sham-graft). Immunohistochemical stainings revealed that the grafted human ES cells survived and expressed TH for at least 6 weeks while the experiment was continued.
Park
Sepill
S
Maria Infertility Hospital Medical Institute/Maria Biotech, Seoul 130-110, South Korea.
Kim
Eun Young
EY
Ghil
Gwang Su
GS
Joo
Wan Seok
WS
Wang
Kyu Chang
KC
Kim
Yong Sik
YS
Lee
Young Jae
YJ
Lim
Jinho
J
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D006136:GTP Cyclohydrolase / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007980:Levodopa / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase