Factors controlling the engraftment of transplanted dog bone marrow cells

Abstract

The LD50 of total body irradiation (TBI) for the bone marrow (BM) syndrome and the gastrointestinal (GI) syndrome was determined in dogs as 3.7 Gy, and 8.5 Gy respectively. Five Gy TBI was adequate conditioning for BM cells of littermate donors identical for the major histocompatibility complex (MHC). The maximum tolerated TBI (about 7.5 Gy) caused more side effects than 5.0 Gy TBI and was insufficient for engraftment of realistic numbers of BM cells of MHC mismatched donors. In autologous and MHC matched transplants, the rate of hemopoietic recovery correlated with the number of BM cells given. Approximately 2 × 107 autologous and 1 × 108 MHC identical BM cells.kg−1 were needed for radiation protection. Platelet recovery was significantly more rapid in allogeneic combinations in comparison to autologous transplants. Low numbers of autologous cryopreserved bone marrow cells were as effective as fresh bone marrow cells in rescuing animals after lethal TBI. Other factors that influence BM cell engraftment were confirmed (prior sensitization of the recipient, donor selection) or identified (purification of BM cells on density gradient and selective gastrointestinal decontamination of the recipient). Consistent engraftment of gradient separated, MHC identical, BM cells was found after conditioning with two fractions of 6.0 Gy TBI, separated by 72 h. One MHC haplotype mismatched marrow did engraft after two TBI fractions of 6.0 Gy. Engraftment no longer occurred with gradient purified bone marrow cells from this type of donor. Late effects of TBI were early greying in all animals, and secondary uterinc inertia in female dogs after 7.5 Gy TBI. Fertility in males or females was not changed by radiation. An increased incidence of pancreas fibrosis was noted in dogs receiving two fractions of 6.0 Gy TBI.