LACK OF EVIDENCE OF PERMANENT ENGRAFTMENT AFTER IN-UTERO FETAL STEM-CELL TRANSPLANTATION IN CONGENITAL HEMOGLOBINOPATHIES

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, In one fetus with alpha-thalassemia, one with sickle cell an emia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11, The fet us with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4x10(8) cells/kg) and in the 31st weeks of gestation (1.2 x10(8) cells/kg), and is now two years of age, One fetus with sickle c ell anemia received its transplant in the 13th week of gestation (16.7 x10(8) cells/kg), and is now one year old, The fetus with beta-thalass emia was transplanted in 18th week (8.6x10(8) cells/kg), and is now th ree months old, Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PC R (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alph a- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 m onths of age, respectively, In neither of these cases were we able to detect convincing evidence of stem cell engraftment, Thus, the adminis tration of fetal stem cells to fetal recipients after the 12th meek of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earli er transplantations and/or higher cell doses.