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Review
. 2012;200:373-404.
doi: 10.1016/B978-0-444-59575-1.00017-X.

Derivation of Striatal Neurons From Human Stem Cells

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Review

Derivation of Striatal Neurons From Human Stem Cells

Pedro Viegas et al. Prog Brain Res. .

Abstract

Huntington's disease cell therapy is for the moment the only therapeutic approach for this devastating neurodegenerative disorder that has demonstrated significant and long-lasting functional benefits in patient. Logistical and biological difficulties associated with the use of human fetal tissue however dramatically reduce the number of patients eligible to this therapy. During the past decade, the exploration of alternative cellular sources, conducted in parallel to the clinical trials, has gradually put forward human pluripotent stem cells as prime candidate for Huntington's disease cell therapy. Protocols for the differentiation of such cells into therapeutically relevant striatal neuron precursors require thorough understanding of the molecular determinant that controls the development of the anterior and ventral part of the forebrain from which the striatum arises. Key secreted molecules that play pivotal roles in the development of these regions in mice have been successfully used to direct the specification of neural derivatives of human pluripotent stem cells. Assessment of the therapeutic potential of resulting striatal grafts has made significant progress in the last 4 years. The proof of principle that human embryonic stem cell derivatives can achieve some degrees of functional striatal repair in a mouse model of Huntington's disease is now established. As in other neurodegenerative diseases such as Parkinson's disease, recent developments have raised hopes for stem cell-based therapy of Huntington's disease.

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