ABSTRACT
I. INTRODUCTION A. Rationale To date, 21 in utero transplants have been reported in humans, 4 of which have been successful, all in immunodeficiency disorders (1-3). Despite this limited initial clinical success in humans, the clinical applications of this procedure are likely going to increase. Although many congenital diseases can be cured by postnatal bone marrow transplantation, there are serious limitations associated with its use (4-8). Allogeneic bone marrow transplantation requires ablation and immunosuppression, which may lead to high-risk, frequently life threatening infections. For many congenital disorders, for which damage occurs in utero, postnatal transplants are frequently too late (4-6). Additionally, there is only 25% chance that a specific patient will have a HLA-matched sibling donor. Even with a matched sibling donor, the risk of graft-versus-host disease (GVHD) is high and is associated with significant mortality and morbidity (9-14). The early gestational fetus is immunologically immature and therefore susceptible to the development of tolerance to specific antigens during its ontogeny. Immunosuppression and myeloablation may not be necessary and therefore alleviate the toxicity and cost of this procedure as compared to the postnatal transplants. If paternal cytokine-stimulated peripheral blood stem cells were to be used, this would provide an unlimited source of donor cells for prenatal transplants and postnatal boosts in tolerant recipients.
