Treatment of human fetuses and induction of immunological tolerance in humans by in utero transplantation of stem cells into fetal recipients.
Since 1976, we have performed more than 240 fetal tissue transplants (FLTs) to treat 63 patients with severe immunodeficiency disease (IDD), with inborn errors of metabolism (IEM), or with severe aplastic anemia. In both IDD and IEM, FLT into postnatal recipients has demonstrated beneficial effects (67%) of the patients were either cured or improved significantly). In 1988, we developed in utero FLT into human fetuses, taking advantage of the immunological tolerance of young fetuses. The transplants have involved fetuses suffering from various diseases at 12-28 weeks postfertilization with 2 of the 6 cases eventually resulting in abortion. With the 4 other fetuses, a favorable outcome was observed: 3 children are now more than 4 years old, and are alive and well with evidence of engraftment, reconstitution of immunity, and partial correction of beta zero thalassemia. In the fourth case, the fetus is alive and well and birth is expected soon. In utero transplantation of stem cells is a therapy with remarkable advantages: (a) tolerance induction due to the immune immaturity of the host, (b) lack of graft-versus-host disease due to the immaturity of the donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) an optimal environment for donor fetal cell development in the vicinity of host fetal cells and growth factors.
Touraine
J L
JL
Department of Transplantation and Clinical Immunology, Hôpital Edouard-Herriot, Lyon, France.
D005260:Female; D005315:Fetal Diseases; D006105:Granulomatous Disease, Chronic / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D007153:Immunologic Deficiency Syndromes / Q000196:embryology / Q000628:therapy*; D008099:Liver / Q000196:embryology*; D008297:Male; D009542:Niemann-Pick Diseases / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D017086:beta-Thalassemia / Q000628:therapy*