In utero hematopoietic stem cell transplantation. A status report.

In utero hematopoietic stem cell transplantation is currently in its early stage of development, but it holds considerable promise as a therapeutic approach for the treatment of a large number of congenital hematologic diseases. Experimental evidence supports the concept of the early gestational fetus as a favorable recipient for cellular therapy. Unique aspects of normal hematologic and immunologic ontogeny allow engraftment and long-term persistence of transplanted hematopoietic stem cells without the requirement for myeloablation or immunosuppression. To date, 21 in utero transplants have been reported. Success has been limited to 4 fetuses, all with immunodeficiency disorders. Despite this limited evidence of clinical efficacy, interest in stem cell transplantation has been gaining momentum, and clinical application is likely to increase. Parallel advances in prenatal diagnosis, fetal intervention, and hematopoietic stem cell technology have removed many of the practical, technical, and ethical obstacles to clinical application. This progress has been accompanied by an increase in the number of centers with both the stated interest and perceived expertise to develop clinical programs. However, there is currently limited consensus among investigators on many important issues, such as the mode or timing of in utero transplantation, the ideal source or dose of donor cells, estimation of maternal and fetal risks, appropriate candidate diseases for treatment, and important ethical considerations in counseling and therapy.