In utero hematopoietic stem cell transplantation. A status report
A. W. Flake and E. D. Zanjani
Department of Surgery, Children's Hospital of Philadelphia, PA 19104, USA. flake@email.chop.edu
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.
