The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution

In mammalian ontogeny, the liver constitutes the primary hematopoietic organ for some time. Fetal liver cells (FLC) are rich in hematopoietic stem cells with a high proliferative potential but contain few post-thymic T cells. In animal studies, FLC restored hematopoiesis without severe graft-versus-host disease. However, genetic disparity between donor and host frequently limited durable engraftment and prevented or protracted complete immune reconstitution in most fully allogeneic recipients. Some children with severe combined immunodeficiency have been cured by FLC infusion, whereas favorable effects in aplastic anemia, acute leukemia, and inborn errors of metabolism have been limited and badly understood. Fetal liver transplantation in animals may serve as a model for the analysis and management of complications associated with the transfer of purified hematopoietic stem cell grafts and aid in the development of future therapeutic strategies requiring rapidly proliferating stem cell populations.     

Repopulating potential of hematopoietic precursor cells

Experiments were performed in 1800 cGy whole-body x-irradiated dogs. Mononuclear cells were collected from bone marrow, peripheral blood, and fetal liver. They were cryopreserved in -196 degrees C liquid nitrogen until used for transplantation. The thawed transfusates were adjusted to contain 1.5-1.6 x 10(5) CFU-GM per kg body weight. The blood granulocyte recovery was rapid after transfusion of blood-derived stem cells as compared to the use of bone-marrow-derived stem cells. In both instances, however, normal values were not reached for several weeks. In contrast, the use of fetal-liver-derived stem cells resulted in a very rapid initial granulocyte increase with a return of values to normal (or even overshoot) within 3 weeks after transplantation. A biomathematical granulocyte renewal simulation system is described that permits calculation of the absolute number of pluripotent stem cells in the transfusate. The data after fetal liver stem cell transplantation can be fitted only if an initial stem cell replication rate of 0.95 is assumed (in contrast to 0.65 using bone marrow or blood-derived stem cells).