In vivo engraftment potential of clinical hematopoietic grafts.
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.
Leung
W
W
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-5001, USA.
Ramírez
M
M
Novelli
E M
EM
Civin
C I
CI
D000328:Adult; D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018826:CD13 Antigens / Q000276:immunology; D002678:Chimera; D006082:Graft Enhancement, Immunologic; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous
D018941:Antigens, CD19; D018952:Antigens, CD34; D018826:CD13 Antigens