In utero transplantation: baby steps towards an effective therapy.

In utero transplantation (IUT) offers the potential to treat a large number of diseases by transplantation of healthy cells into a fetus with a birth defect. Prenatal diagnosis is feasible for many diseases prior to the full development of the fetal immune system offering the opportunity to introduce foreign cells and antigens into the developing fetus. At least 45 cases of IUT have been performed for a variety of diseases. IUT has successfully treated severe combined immunodeficiency and there are indications that it may be effective in treating some nonhematopoietic diseases. However, many diseases remain resistant to fetal therapy owing to the low levels of chimerism that can be achieved. Promising efforts to improve the levels of engraftment are focusing on optimizing the graft and developing donor-specific tolerance in the fetal recipient. Mounting evidence suggests that donor T cells can aid in achieving clinically significant levels of chimerism. The use of fetal donor cells may also offer some benefit. Animal experiments suggest that even low-level chimerism can lead to tolerance, which can be exploited by booster transplants in the neonate. Continued research appears likely to succeed in developing IUT into an effective form of therapy for a variety of diseases.