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.