RRC ID 41978
Author Barberi T, Klivenyi P, Calingasan NY, Lee H, Kawamata H, Loonam K, Perrier AL, Bruses J, Rubio ME, Topf N, Tabar V, Harrison NL, Beal MF, Moore MA, Studer L.
Title Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice.
Journal Nat. Biotechnol.
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 gamma-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.
Volume 21(10)
Pages 1200-7
Published 2003-10
DOI 10.1038/nbt870
PII nbt870
PMID 14502203
MeSH Animals Cell Differentiation / physiology Coculture Techniques / methods* Fertilization Male Mice Neurons / classification Neurons / physiology* Neurons / ultrastructure* Nuclear Transfer Techniques* Parkinsonian Disorders / pathology Parkinsonian Disorders / surgery* Stem Cell Transplantation / methods* Stem Cells / physiology* Stem Cells / ultrastructure* Treatment Outcome
IF 35.724
Times Cited 458
Human and Animal Cells