Virchows Arch. Abt. B Zellpath. 13, 179--195 (1973) 9 by Springer-Verlag 1973 Teratocarcinoma with the Capacity for Differentiation Restricted to Neuro-Ectodermal Tissue* I. Damjanov, D. Solter, and D. ~erman** Department of Pathology and Department of Biology, University of Zagreb, School of Medicine Received April 21, 1973 Summary. A retransplantable murine teratocarcinoma with its capacity for differentiation restricted to neuro-ectodermal derivatives was studied biochemically, histochemically and by means of electron microscopy in order to assess the nature of the stem cells and the somatic tissue that form the tumor. It was found that the stem cells of this monophyletic terato- carcinoma appear ultrastructurally immature and undifferentiated and thus do not differ from the stem cells of an ordinary polymorphous teratocarcinoma i.e. embryonal carcinoma cells. These cells give rise to somewhat more differentiated cells corresponding to the cells of the neural tube. First signs of differentiation are the appearance of tight junctions on the cell membrane and cytoplasmic bridges between adjacent cells through the interruptions on the cell membrane, together with the appearance of cytoplasmic microtubules. The primitive neurogenic cells form rosette like structures but no basement membrane delimits them from the most undifferentiated stem cells on one and the more differentiated neural and glial cells on the other side. Injected intraperitoneally the stem cells of the neurogenic teratocarcinoma do not form embryoid bodies. The neural and glial tissue formed in the tumor is composed predominantly of immature and incompletely differentiated cells, although mature neural and glial cells as well as intermediate cells of varying maturity could also be identified. The level of tissue organization is rather primitive despite the fact that tight glio-neural and glio- vascular connections are formed and synapses and myelinized axons are seen in the tumor. The 100000 g supernatant from the tumor contains the acidic fast migrating protein bands characteristic for the brain, and although not all the protein bands of an adult mouse brain extract could be demonstrated in the tumor, there is a remarkable similarity between the two tissues examined electrophoretically. It was concluded that the neuro-ectodermal tissue formed from the malignant stem cells does not differ basically from normal maturing neural tissue, although it never attains the complex architectural organization of a normal brain. Teratocarcinomas are malignant tumors composed of malignant stem cells which differentiate and thus give rise to various somatic tissues. The stem cells of teratocarcinoma, called in accordance with the concept of Pierce (1967) em- bryonal carcinoma cells, are multipotential and could be considered as malignant equivalents of either normal primordial germ cells (Pierce and Beals, 1964 ; Pierce et al., 1967 ; Stevens, 1967) or multipotential embryonic cells from early stages of development (Stevens, 1970a, b; Damjanov et al., 1971a, b). Experimentally it was indeed possible to grow teratocarcinomas both from primordial germ cells and the pregastrulation embryonic cells (Stevens, 1967, 1970a, b) and the stem cells * This study was supported by the Grant No. IV/3 of the Council for Scientific Affairs of S. R. Croatia, and by NIH PL 480 Research Agreement No. 02-038-1. ** Technical assistance of Miss Durdica Matkun and Miss Vi~nja Cesar is greatfully acknowl- edged. 13 Virchows Arch. Abt. B Zellpath.Bd. 13