LONG-TERM INTEGRATION AND NEURONAL DIFFERENTIATION OF HUMAN EMBRYONALCARCINOMA-CELLS (NTERA-2) TRANSPLANTED INTO THE CAUDOPUTAMEN OF NUDE-MICE

NTera-2 (NT2) cells are a human embryonal carcinoma (EC) cell line der ived from a teratocarcinoma that differentiate exclusively into postmi totic neurons in vitro following retinoic acid (RA) treatment. Like ot her EC cell lines, NT2 cells rapidly form lethal tumors following tran splantation into peripheral sites or many regions of the brain. Howeve r, when grafts are confined to the caudoputamen (CP), the NT2 cells di fferentiate into postmitotic neuronlike cells and do not form lethal t umors. To examine the long-term fate of such grafts, we studied NT2 ce ll transplants in the CP of nude mice that survived for > 1 year. NT2 cells in these grafts acquired molecular markers of fully mature neuro ns including the low, middle, and high molecular weight neurofilament proteins, microtubule-associated protein 2, tau, and synaptophysin. Fu rthermore, neuronlike cells in long-term CP grafts formed synaptic str uctures, and their processes became myelinated, whereas tyrosine hydro xylase (TH)-positive neuronlike cells in the grafts increased with pro gressively longer postimplantation survival times. Soluble extracts of the adult mouse CP augmented TH expression in RA-treated NT2 cells in vitro. These data suggest that the adult mouse CP is a source of fact or(s) that inhibits tumor formation and induce a catecholaminergic neu ronal phenotype in these human NT2 cells in vivo and in vitro. Identif ication of these factors could accelerate efforts to elucidate mechani sms that regulate progenitor cell fate and the commitment of neurons t o specific neurotransmitter phenotypes. (C) 1996 Wiley-Liss, Inc.