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Protocols for Generating ES Cell-Derived Dopamine Neurons

  • Sonja KriksEmail author
  • Lorenz Studer
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 651)

Abstract

Stem cells are defined by their ability to self-renew and to differentiate into specific specialized cell types. Pluripotent stem cells such as embryonic stem cells are capable of differentiating into all cell types of the three germ layers. Self-renewal and differentiation potential are properties that make stem cells an attractive source for cell therapeutic efforts including the treatment of neurological diseases such as Parkinson’s disease (PD). Parkinson’s disease is one of the most common neurological disorders and is characterized by the selective degeneration of dopamine (DA) neurons in the ventral midbrain. The midbrain region contains three groups of DA neurons, the retrorubral field (A8), the tegmental area of the ventral midbrain (VTA, A10) and the substantia nigra pars compacta (A9). Only the latter subgroup is primarily affected in PD and responsible for most of the motor dysfunction. Due to this rather selective loss of DA neurons in the substantia nigra, PD is considered a neurological disease amenable to cell replacement. Cell replacement therapy in PD has been attempted in several hundred patients worldwide using fetal human DA neurons. While promising results have been reported in several open label studies (e.g., 1,2) placebo-controlled clinical trials using human fetal dopamine neurons have yielded modest clinical improvement at best.3,4 Furthermore, a subset of these patients displayed disabling graft-induced dyskinesias. There are many potential reasons for this relatively poor outcome as discussed in detail elsewhere.5 However, the limited availability of donor tissue, the low percentage of DA neurons within fetal grafts and ethical concerns associated with the use of human fetal tissue suggest that alternative cell sources are required for successful clinical translation.

Keywords

Embryonic Stem Cell Dopaminergic Neuron Human Embryonic Stem Cell Dopamine Neuron Mouse Embryonic Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Developmental Biology Program and Department of NeurosurgerySloan-Kettering Institute for Cancer ResearchNew York

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