In Vivo Engraftment Potential of Clinical Hematopoietic Grafts

Abstract

Background: Quantitative assays are needed to characterize the multilineage engraftment potential of clinical hematopoietic grafts. After we observed a dose-response relationship between the number of human hematopoietic cells transplanted into nonobese diabetic-scid/scid (NOD/SCID) mice and the number of human CD45+ cells recovered in the chimeras' marrows and spleens, we sought to develop a multiple linear regression model that allows quantitative comparisons of human cell engraftment in vivo. Methods: We used this NOD/SCID xenotransplant model to compare the engraftment potential of cord blood vs. adult marrow or mobilized blood, after either of 2 commonly used clinical graft engineering procedures: CD34+ cell selection or T cell depletion. Results: The engraftment per transplanted cell was >20 fold higher for cord blood cells, as compared to hematopoietic cells from adults. However, there was no difference in engraftment per CD34+ cell transplanted between marrow and mobilized blood. Levels of human cell engraftment from all sources could be increased by administration of human hematopoietic growth factors to human/mouse chimeras after transplantation. Correlation analysis 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 derived from the same primitive precursor cells. Conclusions: These findings and assay may be useful in the development of clinical hematopoietic cell therapies.