[Intrauterine transplantation of hematopoietic stem cells for therapy of genetic diseases]

Abstract

In utero transplantation of hematopoietic stem cells is a most promising fetal therapy. The aim is to treat a genetic disease prenatally before the onset of irreversible organ damage. As the fetus is immunoincompetent in the first and early second trimester of pregnancy and thus tolerant to foreign antigen, engraftment of transplanted stem cells is possible without rejection and without the need for immunosuppression. Additionally, there is enough space available in the fetal bone marrow for the homing of transplanted stem cells, and the intrauterine environment is protective for the fetus, thus typical complications of postnatal transplantation like graft rejection could be avoided. Good results of in utero treatment of severe congenital immunodeficiencies have been achieved in different animal models as well as in humans. No success, however, has been reported as yet in genetic diseases without immunodeficiency, mainly because it seems to be difficult to achieve a clinically significant level of chimerism. Ongoing research projects are focussed on the search for alternative stem cell sources like umbilical cord blood or fetal liver, optimizing the in vitro stem cell processing by using special enrichment techniques, adding early growth factors to the transplant or expanding stem cells ex vivo and finding the ideal stem cell dose. In non-immunodeficient recipients the "window of opportunity" seems to be exclusively at the end of the first trimester; thus early administration of the transplant is mandatory. Induction of tolerance against donor cells is possible, though the clinical relevance for postnatal transplantation remains to be proven.