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Sustained proliferation, multi‐lineage differentiation and maintenance of primitive human haemopoietic cells in NOD/SCID mice transplanted with human cord blood

Time course studies of sublethally irradiated non‐obese mice with severe combined immunodeficiency (NOD/SCID mice) transplanted intravenously with 107 human cord blood cells showed a rapid and parallel regeneration of human erythroid, granulopoietic, megakaryopoietic and B‐lymphoid progenitors, as well as more primitive subpopulations of CD34+ cells (defined by their multi‐lineage in vitro colony‐forming ability, coexpression of Thy‐1, or functional activity in long‐term culture‐initiating cell [LTC‐IC] assays), in the marrow, spleen and blood. Maximum numbers of human cells were reached within 6 weeks and were then sustained for another 18–20 weeks. 3H‐thymidine suicide studies showed all types of in vitro clonogenic human progenitors tested and the human LTC‐IC to be proliferating in vitro throughout this period. A 2‐week course of injections of human Steel factor, interleukin‐3, granulocyte‐macrophage colony‐stimulating factor and erythropoietin given just prior to assessment of the mice had no effect on any of these human engraftment parameters. 4–6 weeks post‐transplant, the marrow of primary NOD/SCID recipients contained human cells that were able to regenerate lymphopoiesis and/or myelopoiesis in secondary irradiated NOD/SCID mice. These findings establish a baseline for the kinetics of engraftment, multi‐lineage differentiation and self‐renewal of human cord blood stem cells in this xenogeneic transplant model and thus set the stage for future studies of their regulation in vivo.