IN-VIVO ENGRAFTMENT POTENTIAL OF CLINICAL HEMATOPOIETIC GRAFTS

Background: Quantitative assays are needed to characterize the multili neage engraftment potential of clinical hematopoietic grafts, After we observed a dose-response relationship between the number of human hem atopoietic cells transplanted into nonobese diabetic-scid/scid (NOD/SC ID) mice and the number of human CD45+ cells recovered in the chimeras ' marrows and spleens, we sought to develop a multiple linear regressi on model that allows quantitative comparisons of human cell engraftmen t in vivo. Methods: We used this NOD/SCID xenotransplant model to comp are the engraftment potential of cord blood vs. adult marrow or mobili zed blood, after either of 2 commonly used clinical graft engineering procedures: CD34+ cell selection or T cell depletion. Results: The eng raftment per transplanted cell was >20 fold higher for cord blood cell s, as compared to hematopoietic cells from adults. However, there was no difference in engraftment per CD34+ cell transplanted between marro w and mobilized blood. Levels of human cell engraftment from all sourc es could be increased by administration of human hematopoietic growth factors to human/mouse chimeras after transplantation. Correlation ana lysis of the number of human CD13+ myeloid cells and CD19+ B lymphoid cells in the chimeras' marrows 8 weeks after transplantation provided evidence that almost all the human myeloid and B lymphoid cells were d erived from the same primitive precursor cells, Conclusions: These fin dings and assay may be useful in the development of clinical hematopoi etic cell therapies.