Dr. Flake's current studies potentially extend prenatal stem cell transplants to a broader range of diseases, by manipulating conditions to create a competitive advantage for donor cells over host cells. The IUHSCT procedure first makes the recipient's immune system tolerant of low levels of donor cells, and then a second, nontoxic procedure after birth provides a competitive advantage for the transplanted donor cells, allowing them to multiply.
"Performing the stem cell transplant prenatally relies on features of the fetal immune system that are more receptive to transplantation," said Dr. Flake. "For instance, the immaturity of the fetal immune system makes it less able to mount an immune response against the transplanted cells." Paradoxically, the technique also relies on a strength of the fetal immune system: its healthy thymus, a gland that declines in function after puberty. The fetal thymus produces T-regulatory cells, which help to reduce graft-versus-host disease. In that disease, a life-threatening complication of cell and organ transplants, donor cells attack the patient's tissues.
The second, postnatal step of the treatment compromises host blood cells and allows the donor cells to engraft themselves in the recipient's bone marrow and bloodstream. Because the prenatal transplant has made the host animal tolerant of donor cells, the postnatal procedure can be less toxic than conventional treatments that use harsh chemotherapy drugs or high-dose radiation to wipe out the host's existing immune system.