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Protocols for Generating ES Cell-Derived Dopamine Neurons

  • Chapter
Development and Engineering of Dopamine Neurons

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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Authors and Affiliations

  1. Developmental Biology Program and Department of Neurosurgery, Sloan-Kettering Institute for Cancer Research, 1275 York Ave, Box 256, New York, New York, 10065

    Sonja Kriks & Lorenz Studer

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  1. Sonja Kriks
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  2. Lorenz Studer
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Correspondence to Sonja Kriks .

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  1. Rudolf Magnus Institute of Neuroscience Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands

    R. Jeroen Pasterkamp PhD , Marten P. Smidt PhD  & J. Peter H. Burbach PhD ,  & 

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Kriks, S., Studer, L. (2009). Protocols for Generating ES Cell-Derived Dopamine Neurons. In: Pasterkamp, R.J., Smidt, M.P., Burbach, J.P.H. (eds) Development and Engineering of Dopamine Neurons. Advances in Experimental Medicine and Biology, vol 651. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0322-8_10

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