Physicians may one day be able to treat genetic blood diseases before a child is even born. In a study of mice that was published this week in the Journal of Clinical Investigation, researchers at the University of California, San Francisco, have found that transplanting a mother’s own stem cells into her fetus populates its bone marrow with healthy cells while avoiding immune rejection.
If the findings hold true in humans, stem-cell transplants from mother to fetus could prime the fetus for a bone-marrow transplant from its mother—or a donor that is tissue-matched to the mother—after birth.
Diseases such as sickle cell anemia and beta thalassemia result from abnormal red blood cells and can be treated with bone-marrow transplants. But it’s not always possible to find a match. And standard bone-marrow transplants, even between tissue-matched donors, must be followed with a lengthy course of immunosuppressive drugs.
Scientists theorize that bone-marrow transplants performed when a fetus is still developing would override this problem. They suspect that the fetus’s immature immune system could be tricked into adopting those foreign cells and recognizing them as its own. “The fetus is wired to tolerate cells—when it encounters cells from mom, it tolerates them,” says Tippi MacKenzie, the pediatric surgeon at UCSF who led the new research.
Research in animals has shown the promise of that approach. But early tests in humans came up against a serious setback—the donor cells were being rejected and killed off before a fetus could assimilate them, and no one was quite sure why. “It’s a conundrum,” says MacKenzie.
The blame, it seems, may be mom’s. MacKenzie and her colleagues found that when they injected a fetus with hematopoietic stem cells (which populate bone marrow and give rise to blood cells) that were not matched to the mother or fetus, the infusion prompted an influx of maternal immune cells into the fetus.