Embryonic stem cell-derived neuronally committed precursor cells with reduced teratoma formation after transplantation into the lesioned adult mouse brain

¹ Zentrum für Molekulare Neurobiologie, Universität Hamburg, Falkenried 94, 20251 Hamburg, Germany; Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
² Zentrum für Molekulare Neurobiologie, Universität Hamburg, Falkenried 94, 20251 Hamburg, Germany
³ Institute of Neuropathology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany

^* To whom correspondence should be addressed. E-mail: marcel.dihne{at}uni-duesseldorf.de.

	Abstract

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. While teratoma formation rarely occurs in xenogeneic transplantation paradigms of ES cellderived 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 embryonic stem cell-derived neural aggregates (SENAs) that consist predominantly of neuronally committed precursor cells. Purified SENAs that were differentiated into immature but post-mitotic neurons did not form tumors up to four months after syngeneic transplantation into the acutely degenerated striatum and showed robust survival.