“What we saw was that it’s not the fetal immune system that’s rejecting the cells—it’s the mother’s,” MacKenzie says. “And if it’s the mother’s immune system that’s rejecting them, we may be able to transplant maternal cells for some of these disorders and get them to engraft.” Indeed, when researchers injected the fetus with stem cells from a donor that was tissue-matched to the mother, the cells happily took root in the fetus’s bone marrow.
“The critical question is how this applies to large animals and humans,” says Alan Flake, a pediatric surgeon and the director of the Center for Fetal Research at the Children’s Hospital of Philadelphia. Part of the issue with humans is that even when adult stem cells do survive in the fetus, it’s difficult for them to compete with the resident fetal stem cells, which can proliferate much more rapidly.
But Flake, who pioneered the fetal-stem-cell transplant treatment for severe combined immunodeficiency disease (SCID), or “bubble boy syndrome,” says that although a single dose of maternal or maternally matched donor cells might not cure disease, it could prime the fetus’s immune system into accepting a stem-cell transplant from the same person later in life. (Fetal transplants work in SCID because the disease causes such a severe lack of immunity that a fetus can fully incorporate stem-cell transplants without competition from preëxisting immune cells.)
“This might allow us to perform in-utero transplantation to fetuses in a way that is more likely to work, and to do it in a way that could be safer to the fetus,” says Joseph (Mike) McCune, a professor of experimental medicine at UCSF who was not involved in the study.
The next step, MacKenzie says, will be to test the treatment in larger mammals and nonhuman primates. But for now, her lab is more focused on understanding precisely what’s going on in the maternal-fetal immune system interactions. “We’re trying to figure out the mechanism by which the mother cells are exerting their effect. And we’re looking at the idea of immune-cell trafficking between mom and fetus—to what extent does it happen in human pregnancies?”