title: Embryonic stem cell-derived neuronally committed precursor cells with reduced teratoma formation after transplantation into the lesioned adult mouse brain.
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. 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.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Germany. marcel.dihne@uni-duesseldorf.de
authors.forename: Marcel
authors.initials: M
authors.lastname: Dihné
authors.forename: Christian
authors.initials: C
authors.lastname: Bernreuther
authors.forename: Christian
authors.initials: C
authors.lastname: Hagel
authors.forename: Kai O
authors.initials: KO
authors.lastname: Wesche
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000517:prevention & control; D016380:Brain Tissue Transplantation / Q000009:adverse effects / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013724:Teratoma / Q000517:prevention & control; D014185:Transplantation, Isogeneic
chemical_list: D016222:Fibroblast Growth Factor 2