Sustained Macroscopic Engraftment of Cynomolgus Embryonic Stem Cells In Xenogeneic Large Animals After In Utero Transplantation

Because embryonic stem (ES) cells are able to proliferate indefinitely and differentiate into any type of cell, they have the potential for providing an inexhaustible supply of transplantable cells or tissues. However, methods for the in vitro differentiation of human ES cells are still quite limited. One possible strategy would be to generate differentiated cells in vivo. In view of future clinical application, we investigated the possibility of using xenogeneic large animals for this purpose. We transplanted nonhuman primate cynomolgus ES cells into fetal sheep at 43–67 gestational days (full term 147 days, n = 15). After birth, cynomolgus tissues, which were mature teratomas, had been engrafted in sheep when more than 1 × 106 ES cells were transplanted at <50 gestational days. Despite the sustained engraftment, both cellular and humoral immune responses against the ES cells were detected, and additional transplantation was not successful in the animals. At 2 weeks post-transplantation, the ES cell prog...