Gender dependent survival of allogeneic trophoblast stem cells

Abstract

Pregnancy succeeds because the fetal allograft survives in the presence of a fully functional maternal immune system. The placenta, especially its trophoblast, provides the initial barrier between the maternal and fetal environment and, due to their location, trophoblast cells could be expected to be immune-privileged. Yet in the ectopic sites tested thus far, trophoblast stem cell transplants have failed to show noticeable immune privilege and appear to lack physiological support. However in this study, portal vein injected green fluorescent protein-labeled trophoblast stem cells were able to survive for several months in the livers of allogeneic female (14/14), but not male (0/4), mice. Gonadectomy experiments revealed that this gender-dependent survival does not require the presence of ovarian hormones (4/4) but the absence of testicular factors (5/5). In contrast, similarly labeled allogeneic embryonic stem cells were reliably rejected (11/11); these same embryonic stem cells survived when mixed with unlabeled trophoblast stem cells (13/13). The protective effect offered by the trophoblast stem cells did not require any immunological similarity with the co-injected embryonic stem cells. Neither the trophoblast stem cells nor the co-injected embryonic stem cells gave rise to tumors during the study period. Thus, this study demonstrates that, provided a suitable location and hormonal context, ectopic trophoblast stem cells may exhibit and confer immune privilege. These findings suggest applications in cell and gene therapy as well as provide a new model for studying trophoblast physiology and immunology.