Trailblazers

Mother’s Immune System Blocks Fetal Therapies

In utero hematopoietic cell transplantation (IUHCT) introduces donor cells to a fetus to establish a tolerance for later organ or cellular transplant to treat blood diseases, but the tolerance to later transplants is often inconsistent, suggesting an immune barrier sometimes acts against transplanted cells. An animal study led by Alan Flake, MD, the Ruth M. and Tristram C. Colket Jr. Endowed Chair in Pediatric Surgery, found that while mice nursed by foster mothers retained healthy donor cells transplanted using IUHCT, mice nursed by their biological mothers lost the transplanted donor cells. Published in the Journal of Clinical Investigation, the study shows that the mothers whose fetuses received the donor cell transplants had developed antibodies against the transplanted cells and transmitted the antibodies to their pups through breast milk. Although additional research is needed to understand how these findings apply to humans, this study suggests that transplant techniques that avoid the maternal immune response may allow scientists to treat blood diseases before birth.

Merianos DJ, Tiblad E, Santore MT, Todorow CA, Laje P, Endo M, Zoltick PW, Flake AW. Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in mice. J Clin Invest. 2009 Sep;119(9):2590-600.
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