Mixed lymphocyte culture reactivity of fetal baboons: Application for in utero bone marrow transplantation

Bone marrow transplantation offers a potential cure for patients suffering from genetic diseases such as inborn errors of metabolism. The optimal time to transplant many of these affected individuals would be early in gestation. To date, little information is available on the cellular immune reactivity of fetal primate lymphocytes. Therefore, we tested peripheral blood lymphocytes obtained in utero from baboon fetuses (Papio sp.) for their ability to respond in mixed lymphocyte culture (MLC) against their mothers, against a pool of unrelated animals, and in the case of fetuses given unrelated bone marrow transplants in utero, against their specific bone marrow donors. The majority of fetuses as young as 80 gestational days (182-day normal gestation period) were capable of responding strongly to maternal and unrelated lymphocytes in MLC. Of six fetuses that were transplanted, three did not engraft as indicated by undetectable levels of the donor-specific type B allele of glucose phosphate isomerase in fetal blood samples 1 month post-transplant. The three fetuses that did engraft all lost their grafts before birth. These data demonstrate that fetal lymphocytes obtained in utero can be tested for MLC reactivity and suggest that MLC testing can be used to select appropriate donor-recipient combinations for in utero bone marrow transplantation.