Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model
Lars Björklund,Rosario Sanchez-Pernaute,Sangmi Chung,Therese Andersson,Therese Andersson,Iris Y. Chen,Kevin St. P. McNaught,Anna-Liisa Brownell,Bruce G. Jenkins,Claes Wahlestedt,Kwang-Soo Kim,Ole Isacson +11 more
TLDR
It is shown that transplanting low doses of undifferentiated mouse embryonic stem cells into the rat striatum results in a proliferation of ES cells into fully differentiated DA neurons that can restore cerebral function and behavior in an animal model of Parkinson's disease.Abstract:
Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. We show that transplanting low doses of undifferentiated mouse embryonic stem (ES) cells into the rat striatum results in a proliferation of ES cells into fully differentiated DA neurons. ES cell-derived DA neurons caused gradual and sustained behavioral restoration of DA-mediated motor asymmetry. Behavioral recovery paralleled in vivo positron emission tomography and functional magnetic resonance imaging data demonstrating DA-mediated hemodynamic changes in the striatum and associated brain circuitry. These results demonstrate that transplanted ES cells can develop spontaneously into DA neurons. Such DA neurons can restore cerebral function and behavior in an animal model of Parkinson's disease.read more
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Journal ArticleDOI
Parkinson's disease: Mechanisms and models
TL;DR: PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.
Journal ArticleDOI
Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease
Jong-Hoon Kim,Jonathan M. Auerbach,José A. Rodríguez-Gómez,Iván Velasco,Denise K. Gavin,Nadya Lumelsky,Sang-Hun Lee,John Bang Nguyen,Rosario Sanchez-Pernaute,Krys S. Bankiewicz,Ronald D.G. McKay +10 more
TL;DR: It is shown that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells and the dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain.
Journal ArticleDOI
Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease
Marius Wernig,Jian Ping Zhao,Jan Pruszak,Eva Hedlund,Dongdong Fu,Frank Soldner,Vania Broccoli,Martha Constantine-Paton,Ole Isacson,Rudolf Jaenisch +9 more
TL;DR: It is shown that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture and demonstrating the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model.
Journal ArticleDOI
Embryonic stem cells.
Helen J. Rippon,Anne E. Bishop +1 more
TL;DR: This work reviews the history of murine and human ES cell Lines, including practical and ethical aspects of ES cell isolation from pre‐implantation embryos, maintenance of undifferentiated ES cell lines in the cell culture environment, and differentiation of ES cells in vitro and in vivo into mature somatic cell types.
Journal ArticleDOI
Stem cell therapy for human neurodegenerative disorders-how to make it work.
TL;DR: Findings raise hope for the development of stem cell therapies in human neurodegenerative disorders and need to know much more about how to control stem cell proliferation and differentiation into specific phenotypes, induce their integration into existing neural and synaptic circuits, and optimize functional recovery in animal models closely resembling the human disease.
References
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Embryonic Stem Cell Lines Derived from Human Blastocysts
James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
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