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EMBRYONIC STEM CELLS

Embryonic Stem Cell-Derived Neuronally Committed Precursor Cells with Reduced Teratoma Formation After Transplantation into the Lesioned Adult Mouse Brain

^a Zentrum für Molekulare Neurobiologie, Universität Hamburg, Hamburg, Germany;
^b Department of Neurology, Heinrich-Heine-University, Duesseldorf, Germany;
^c Institute of Neuropathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Key Words. Cellular proliferation • Stem cell transplantation • Neural differentiation • Embryonic stem cells • Committed progenitors • Cellular therapy

Correspondence: Marcel Dihné, M.D., University of Düsseldorf – Neurology, Moorenstrasse 5, 40225 Düsseldorf, Germany. Telephone: +00491752741681; Fax: _492118 1184 69; e-mail: marcel.dihne{at}uni-duesseldorf.de

Received August 26, 2005; accepted for publication January 25, 2006.

The therapeutic potential of embryonic stem (ES) cells in neurodegenerative disorders has been widely recognized, and methods are being developed to optimize culture conditions for enriching the cells of interest and to improve graft stability and safety after transplantation. Whereas teratoma formation rarely occurs in xenogeneic transplantation paradigms of ES cell-derived neural progeny, more than 70% of mice that received murine ES cell-derived neural precursor cells develop teratomas, thus posing a major safety problem for allogeneic and syngeneic transplantation paradigms. Here we introduce a new differentiation protocol based on the generation of substrate-adherent ES cell-derived neural aggregates (SENAs) that consist predominantly of neuronally committed precursor cells. Purified SENAs that were differentiated into immature but postmitotic neurons did not form tumors up to four months after syngeneic transplantation into the acutely degenerated striatum and showed robust survival.

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