In utero allogeneic hematopoietic stem cell transplantation to induce tolerance

We studied the efficacy of in utero hematopoietic stem cell transplantation and the ability of such transplantation to induce tolerance in a fetal normal mouse allogeneic model. In 9 of the 162 surviving recipients (5.6%), cells of donor origin were detected after birth. The highest engraftment rate was achieved by transplanting fetal liver cells in a relatively high dose (> 10(6) cells/fetal gram). Skin grafting was performed to determine the presence of prenatally induced tolerance. Only those mice which showed evidence of chimerism became tolerant to skin derived from the prenatal donor's strain while remaining competent to reject a skin transplant from a third strain. Tolerant mice could have significant chimerism reestablished by utilizing monoclonal antibody specific for the recipient H-2 antigen as conditioning for IV fetal stem cell retransplantation.