In utero fetal liver cell transplantation in the treatment of immunodeficient or thalassemic human fetuses.

Following 18 years' experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutic method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The four fetuses that we treated were 28, 26, 17 and 12 weeks of gestation. The first two patients had immunodeficiencies, the two others had thalassemia major. Donor cells were obtained from 7- to 12-week-old fetuses, with conditions approved by the National Committee for Bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of three patients and injected intraperitoneally into the other one, under ultrasonic visualization. The first patient, born in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% then 26% of lymphocytes of donor origin (with distinct phenotype), T-cell responses to tetanus toxoid, CMV and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989; donor cell engraftment has been proven (Y-chromosome in this female patient) and immunological reconstitution is in progress, allowing a normal life at home. The third patient also has evidence of donor cell take (Y-chromosome in a female patient) and a partial effect on thalassemia has been documented (donor hemoglobin present in peripheral blood). In all three cases, no side-effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)