IN-UTERO TRANSPLANTATION OF HEMATOPOIETIC STEM-CELLS FOR THE CORRECTION OF GENETIC-DISEASES

In utero transplantation of hematopoietic stem cells is a most promisi ng fetal therapy, The aim is to treat a genetic disease prenatally bef ore the onset of irreversible organ damage. As the fetus is immunoinco mpetent 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 marr ow for the homing of transplanted stem cells, and the intrauterine env ironment is protective for the fetus, thus typical complications of po stnatal transplantation like graft rejection could be avoided. Good re sults of in utero treatment of severe congenital immunodeficiencies ha ve been achieved in different animal models as well as in humans. No s uccess, 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 umbi lical cord blood or fetal liver, optimizing the in vitro stem cell pro cessing by using special enrichment techniques, adding early growth fa ctors to the transplant or expanding stem cells ex vivo and finding th e ideal stem cell dose. In non-immunodeficient recipients the ''window of opportunity'' seems to be exclusively at the end of the first trim ester; thus early administration of the transplant is mandatory. Induc tion of tolerance against donor cells is possible, though the clinical relevance for postnatal transplantation remains to be proven.