In utero stem cell transplantation.

In utero haematopoietic cell transplantation (IUHCT) is a promising approach for the treatment of a variety of genetic disorders. The rationale is to take advantage of normal events during haematopoietic and immunological ontogeny to facilitate allogeneic haematopoietic engraftment. Strategies that will be discussed include the direct achievement of therapeutic levels of donor cell engraftment by IUHCT, the achievement of adequate levels of engraftment to donor-specific tolerance by IUHCT, followed by postnatal non-myeloablative regimens to enhance levels of donor cell engraftment into the therapeutic range. Although in utero haematopoietic cell transplantation has been clinically successful in severe combined immunodeficiency disease (SCID), it has been unsuccessful in target disorders where there is not a selective advantage for donor cells. This chapter presents the recognized barriers to engraftment in the fetus and discusses promising experimental strategies to overcome these barriers.