Fetal liver transplantation in the dog. I. Restoration of hemopoiesis with cryopreserved fetal liver cells from DLA-identical siblings.

Fetal liver cells (FLC) were obtained from beagle fetuses 52 days postconception, and were cryopreserved prior to transplantation into ten sibling recipients that had previously been exposed to total-body irradiation delivered in 3 fractions of 6 Gy each at 4 days, 2 days, and 2 hr before grafting. Donors and hosts were genotypically identical for dog leukocyte antigens (DLA)-A, B, and D. A rapid and lasting engraftment was achieved in all animals following the transfer of 0.2 X 10(8) to 1.6 X 10(8) mononuclear FLC/kg body weight, which were equivalent to 0.9 X 10(4) to 19.8 X 10(4) granulocyte/macrophage progenitor cells (CFU-GM)/kg. Between days 14 and 20 posttransplant pretreatment levels were detected for blood granulocytes, between days 23 and 28 for circulating platelets, and between days 35 and 40 for the erythrocyte count and hemoglobin concentration. Increasing the number of CFU-GM transfused resulted in an accelerated granulocyte and platelet recovery. Bone marrow cells were of donor origin throughout the observation interval, but declining proportions of host lymphocytes circulated in the peripheral blood during the initial recovery phase. In two dogs, skin alterations that might indicate slight graft-versus-host disease (GVHD) were noted following days 20 and 70, respectively. Six recipients had to be sacrificed due to inanition, probably secondary to radiation-induced pancreatic insufficiency two to three months after grafting. The results of this study indicate that cryopreserved FLC are highly effective in restoring hemopoiesis in DLA-compatible sibling dogs. Transplantation of canine FLC may prove valuable in analyzing mechanisms pathogenetically related to graft rejection or to the development of GVHD following the transfer of T-cell-depleted hemopoietic grafts at a preclinical stage.