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TRANSLATIONAL AND CLINICAL RESEARCH

Neural Stem Cell Model for Prion Propagation

^aInstitut de Génétique Humaine, CNRS-UPR1142, Montpellier, France;
^bLaboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA

Key Words. Neural stem cells • Prions • Neural differentiation • Diagnosis

Correspondence: Sylvain Lehmann, M.D., Ph.D., Institut de Génétique Humaine, CNRS-UPR1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. Telephone: +33-499619931; Fax: +33-499619901; e-mail: Sylvain.Lehmann{at}igh.cnrs.fr; or Ollivier Milhavet, Ph.D., Institut de Génétique Humaine, CNRS-UPR1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. Telephone: +33-499619930; Fax: +33-499619901; e-mail: Ollivier.Milhavet{at}igh.cnrs.fr

Received February 14, 2006; accepted for publication May 25, 2006.
First published online in STEM CELLS EXPRESS   June 1, 2006.



The study of prion transmission and targeting is a major scientific issue with important consequences for public health. Only a few cell culture systems that are able to convert the cellular isoform of the prion protein into the pathologic scrapie isoform of the prion protein (PrP^Sc) have been described. We hypothesized that central nervous system neural stem cells (NSCs) could be the basis of a new cell culture model permissive to prion infection. Here, we report that monolayers of differentiated fetal NSCs and adult multipotent progenitor cells isolated from mice were able to propagate prions. We also demonstrated the large influence of neural cell fate on the production of PrP^Sc, allowing the molecular study of prion neuronal targeting in relation with strain differences. This new stem cell-based model, which is applicable to different species and to transgenic mice, will allow thoughtful investigations of the molecular basis of prion diseases, and will open new avenues for diagnostic and therapeutic research.

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