Background: In utero transplantation (IUT) of hematopoietic stem cells has the potential to treat a large number of hematologic and metabolic diseases amenable to partial replacement of the hematopoietic system.
Methods: A review of the literature was conducted that focused on the clinical and experimental experience with IUT and, in this context, the development of the hematopoietic and immune systems.
Results: Successful application of IUT has been limited to the treatment of various types of immunodeficiencies that affect lymphocyte development and function. Other congenital defects such as the thalassemias have not resulted in clinically significant engraftment. Recent efforts at understanding and overcoming the barriers to engraftment in the fetus have focused on providing a selective advantage to donor stem cells and fostering immune tolerance toward the donor cells. The critical cellular components of the graft that promote engraftment and tolerance induction are being evaluated in animal models. Improvements in engraftment have resulted from the inclusion of T cells and/or dendritic cells in the graft, as well as a strategy of combined prenatal and postnatal transplantation.
Conclusions: The advantages, necessity, and benefits of early treatment will continue to encourage development of IUT as a means to treat hematopoietic and other types of birth defects.