Fetal liver cell transplantation for the creation of lymphohematopoietic chimerism in fetal baboons

OBJECTIVE: Our purpose was to create xenogeneic lymphohematopoietic chimerism by in utero transplantation of human fetal liver cells in the midgestation fetal baboon. STUDY DESIGN: Human fetal liver cell suspensions obtained from preimmune human fetuses (>80 daysʹ gestation) were injected into the peritoneal cavity of three fetal baboons (85, 95, and 104 daysʹ gestation). A total of 9 × 106 cells, in a volume of 1 ml, were injected percutaneously into the fetal abdominal cavity under ultrasonographic guidance. The success of the injection was assessed by observing ascites and free loops of fetal bowel after injection. Fetal umbilical cord blood (35 days posttransplantation) and neonatal blood and bone marrow were obtained to be assayed for the presence of donor hematopoietic cells. Chimerism was detected by fluorescence in situ hybridization with a human Y-chromosome specific probe. RESULTS: All the animals survived the in utero procedures. Thirty-five days transplantation engraftment was noted in one animal. Postnatally the same animal showed engraftment in both the peripheral blood and bone marrow. The rate of chimerism was 1.5% (1.5% of the cells were human) in both the peripheral blood and bone marrow. CONCLUSIONS: This study demonstrates that creation of xenogeneic lymphohematopoietic chimerism is possible in the midgestation fetal baboon. However, the level of chimerism was too low to study the biologic activity of the transplanted cells or to potentially ameliorate lymphohematopoietic disorders. Future studies using allogeneic tissue, evaluating cells obtained from both fetal and adult donors, and comparisons between purified stem cells and fetal liver cells are needed.