IMPROVED ENGRAFTMENT OF HUMAN HEMATOPOIETIC-CELLS IN SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE CARRYING HUMAN CYTOKINE TRANSGENES

We have generated immunodeficient scid(-)/scid(-) (SCID)-transgenic mi ce expressing the genes for human interleukin 3, granulocyte/macrophag e-colony stimulating factor, and stem cell factor. We have compared en graftment and differentiation of human hematopoietic cells in transgen ic SCID mice with two strains of nontransgenic SCID mice. Human bone m arrow cells carrying the CD34 antigen or human umbilical cord blood we re injected into sublethally irradiated recipients. Human DNA was dete cted by polymerase chain reaction in peripheral blood and bone marrow of 14 of 28 transgenic SCID mice after transplantation, but in only 2 of 15 nontransgenic SCID littermates at a 10-fold lower level. Bone ma rrow cultures 8 wk after transplantation of cord blood gave rise to hu man burst-forming unit erythroid, colony-forming unit granulocyte/macr ophage, or granulocyte/erythroid/macrophage/megakaryocyte colonies. En graftment was observed for up to 6 mo in transgenic SCID mice, twice a s long as nontransgenic littermates or previous studies in which trans planted SCID mice were given daily injections of growth factors. We co nclude that the level and duration of engraftment of human cells in SC ID mice can be improved by expression of human cytokine transgenes and that transgenic SCID mice are an efficient model system for the study of human hematopoiesis.