The Effect of Cells Transferred Into the Mouse Blastocyst on Subsequent Development

Abstract

Bone marrow cells from CBA T6T6 mice and testicular teratocarcinoma cells from 129 SvSl mice were transferred into blastocysts from random-bred Swiss albino mice. The blastocysts were allowed to develop in foster mothers and the adults resulting from these blastocysts were studied for evidence of an effect of the transferred cells. A total of 137 adults resulted from the experiments, and one of the mice that had received teratocarcinoma cells in the blastocyst stage showed several thin stripes of agouti hair. All the adult animals received grafts of skin from animals identical to those supplying the cells. In all cases the animals that resulted from blastocysts into which cells had been transferred maintained skin grafts for a significantly longer period than controls. In a number of cases the graft developed agouti hair and in two cases the graft was maintained for approximately 2 mo. These experiments indicate that the transferred cells were able to establish small colonies in the embryos and that some of these cells persisted into the adult.

Self-renewal of teratocarcinoma and embryonic stem cells

“…These undifferentiated cells can also be cultured in vitro to give rise to lines of EC cells (Finch and Ephrussi, 1967). Interestingly, although EC cells form malignant teratocarcinomas when transplanted to ectopic sites, when reintroduced into a blastocyst, they may sometimes become incorporated into the embryo and contribute to tissues of the developing fetus (Brinster, 1974). This indicates that the proliferation of undifferentiated EC cells can be brought under control in response to the appropriate environmental cues.…”

Tumorigenicity of embryonal carcinoma as an assay to study control of malignancy by the murine blastocyst.

“…This proved to be the case because when embryonal carcinoma cells were injected into mouse blastocysts and the injected blastocysts were put into the uteri of pseudopregnant mice, chimeric mice were born, as evidenced by the coat colors of the animals (11).…”

“…In 1974, Brinster (11) reasoned that because embryonal carcinoma appeared to be the equivalent of embryonic epithelium of the mouse blastula (41/2 days of gestation), possibly the environment of the early embryo might be able to regulate the differentiation of embryonal carcinoma cells. This proved to be the case because when embryonal carcinoma cells were injected into mouse blastocysts and the injected blastocysts were put into the uteri of pseudopregnant mice, chimeric mice were born, as evidenced by the coat colors of the animals (11).…”

The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach

“…This suggests that approaches to cancer therapy should be sought that do not involve cell kill; one such approach envisions the conversion of malignant cells through induced differentiation to benign forms with no proliferative potential. This approach assumes that malignancy is not an irreversible state, as has been demonstrated with a variety of tumour types, including teratocarcinomas (Pierce & Wallace, 1971;Brinster, 1974), neuroblastomas (Schubert et al, 1971;Prasad, 1983) squamous cell carcinomas (Pierce & Wallace, 1971), leukaemias (Metcalf et al, 1969;Paran et al, 1970;Gootwine et al, 1982), and adenocarcinomas of the breast (Decosse et al, 1973;Pierce et al, 1977). The use of differentiation as a therapeutic approach also presumes that cancer is a disease of altered maturation.…”