In utero as a potential location for cell transplantation

A variety of diseases, including some which affect the hemostatic and blood coagulation systems, result from dysfunction of specific cell types. Attempts to ameliorate such diseases by implantation of healthy donor cells typically fail due to immune rejection of the donor cells. One method to possibly overcome this limitation is to administer donor cells prior to immune competence, thus inducing immune tolerance to the donated cells. To accomplish this, donor cells must be administered in utero, relatively early in the developmental process. We describe herein studies in which engraftments of fetal hepatocytes and a hepatoblast line were successfully accomplished by in utero administration of cells in mice. This approach reversed the clinical outcome of Factor X (FX) deficiency, increasing the survival time of FX null mice. Further, engraftment of donor cells was observed in the liver, as well as the spleen, brain, interstitium of the gonad, and lung. These results demonstrate the potential for application of in utero administration of fetal or blast cells for correction of disease related to specific cell or tissue dysfunction. The potential for ectopic engraftment suggests that this approach requires further refinement.