Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. 2008

Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
Institut National de la Santé et de la Recherche Médicale/Université d'Evry-Val-d'Essonne Unité Mixte de Recherche 861, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Association Française contre les Myopathies, 91030 Evry, France.

Substitutive cell therapy using fetal striatal grafts has demonstrated preliminary clinical success in patients with Huntington's disease, but the logistics required for accessing fetal cells preclude its extension to the relevant population of patients. Human embryonic stem (hES) cells theoretically meet this challenge, because they can be expanded indefinitely and differentiated into any cell type. We have designed an in vitro protocol combining substrates, media, and cytokines to push hES cells along the neural lineage, up to postmitotic neurons expressing striatal markers. The therapeutic potential of such hES-derived cells was further substantiated by their in vivo differentiation into striatal neurons following xenotransplantation into adult rats. Our results open the way toward hES cell therapy for Huntington's disease. Long-term proliferation of human neural progenitors leads, however, to xenograft overgrowth in the rat brain, suggesting that the path to the clinic requires a way to switch them off after grafting.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006816 Huntington Disease A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4) Huntington Chorea,Juvenile Huntington Disease,Akinetic-Rigid Variant of Huntington Disease,Chorea, Chronic Progressive Hereditary (Huntington),Chronic Progressive Hereditary Chorea (Huntington),Huntington Chronic Progressive Hereditary Chorea,Huntington Disease, Akinetic-Rigid Variant,Huntington Disease, Juvenile,Huntington Disease, Juvenile-Onset,Huntington Disease, Late Onset,Huntington's Chorea,Huntington's Disease,Juvenile-Onset Huntington Disease,Late-Onset Huntington Disease,Progressive Chorea, Chronic Hereditary (Huntington),Progressive Chorea, Hereditary, Chronic (Huntington),Akinetic Rigid Variant of Huntington Disease,Chorea, Huntington,Chorea, Huntington's,Huntington Disease, Akinetic Rigid Variant,Huntington Disease, Juvenile Onset,Huntington Disease, Late-Onset,Juvenile Onset Huntington Disease,Late Onset Huntington Disease
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014183 Transplantation, Heterologous Transplantation between animals of different species. Xenotransplantation,Heterograft Transplantation,Heterografting,Heterologous Transplantation,Xenograft Transplantation,Xenografting,Transplantation, Heterograft,Transplantation, Xenograft
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D017378 Quinolinic Acid A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS. Quinolinate,Quinolinic Acid, Copper(2+) Salt,Quinolinic Acid, Disodium Salt,Quinolinic Acid, Strontium Salt

Related Publications

Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
June 1991, Pharmacology, biochemistry, and behavior,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
January 2018, Methods in molecular biology (Clifton, N.J.),
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
October 2006, The European journal of neuroscience,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
April 2012, Cell stem cell,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
July 2010, Stem cells and development,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
February 2004, The European journal of neuroscience,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
January 2014, Neuroscience letters,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
November 1996, Brain research,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
March 2010, Journal of neuropathology and experimental neurology,
Laetitia Aubry, and Aurore Bugi, and Nathalie Lefort, and France Rousseau, and Marc Peschanski, and Anselme L Perrier
December 1998, Journal of chemical neuroanatomy,
Copied contents to your clipboard!