Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice Journal Article
| Authors: | Barberi, T.; Klivenyi, P.; Calingasan, N. Y.; Lee, H.; Kawamata, H.; Loonam, K.; Perrier, A. L.; Bruses, J.; Rubio, M. E.; Topf, N.; Tabar, V.; Harrison, N. L.; Beal, M. F.; Moore, M. A. S.; Studer, L. |
| Article Title: | Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice |
| Abstract: | Existing protocols for the neural differentiation of mouse embryonic stem (ES) cells require extended in vitro culture, yield variable differentiation results or are limited to the generation of selected neural subtypes. Here we provide a set of coculture conditions that allows rapid and efficient derivation of most central nervous system phenotypes. The fate of both fertilization- and nuclear transfer-derived ES (ntES) cells was directed selectively into neural stem cells, astrocytes, oligodendrocytes or neurons. Specific differentiation into γ-aminobutyric acid (GABA), dopamine, serotonin or motor neurons was achieved by defining conditions to induce forebrain, midbrain, hindbrain and spinal cord identity. Neuronal function of ES cell-derived dopaminergic neurons was shown in vitro by electron microscopy, measurement of neurotransmitter release and intracellular recording. Furthermore, transplantation of ES and ntES cell-derived dopaminergic neurons corrected the phenotype of a mouse model of Parkinson disease, demonstrating an in vivo application of therapeutic cloning in neural disease. |
| Keywords: | signal transduction; controlled study; treatment outcome; nonhuman; animal cell; mouse; phenotype; electron microscopy; animals; mice; cell survival; embryo; animal experiment; animal model; stem cell transplantation; cell differentiation; neurons; in vitro study; biotechnology; cell type; animalia; molecular cloning; cell culture; spinal cord; measurement; stem cells; mesencephalon; drug therapy; nerve function; forebrain; rhombencephalon; dopamine; dopaminergic nerve cell; neurology; embryo transfer; serotonin; coculture techniques; cells; 4 aminobutyric acid; neurotransmitter release; parkinsonism; neurotransmitter; cell nucleus transplantation; parkinsonian disorders; nuclear transfer techniques; parkinsonia; neural differentiation; fertilization; male; priority journal; article |
| Journal Title: | Nature Biotechnology |
| Volume: | 21 |
| Issue: | 10 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2003-10-01 |
| Start Page: | 1200 |
| End Page: | 1207 |
| Language: | English |
| DOI: | 10.1038/nbt870 |
| PUBMED: | 14502203 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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