The maternal immune response inhibits the success of in utero hematopoietic cell transplantation

Abstract

In utero hematopoietic cell transplantation (IUHCTx) is a promising strategy for the treatment of congenital stem cell disorders. Despite the purported immaturity of the fetal immune system, the clinical success of this strategy has been limited by poor engraftment of transplanted cells. The fetal host immune system is thought to be the major barrier to achieving successful IUHCTx. Since the fetal immune system is immature, however, we hypothesized that the maternal immune response may instead pose the true barrier to IUHCTx. We have demonstrated that maternal T cells traffic into the fetus after allogeneic in utero transplantation and that these lymphocytes play a critical role in limiting engraftment. Furthermore, we have shown that MHC matching the donor cells to the mother improves engraftment in the unmatched fetus. These results help renew interest in using the fetal environment to treat patients with congenital stem cell disorders.