A preclinical xenotransplantation animal model to assess human hematopoietic stem cell engraftment.

Delayed megakaryocytic engraftment occurs in approximately 8 percent of patients undergoing autologous transplantation with PBPCs, and a reliable assay to predict engraftment is not yet available. The correlation between human cell engraftment in a mouse xenotrans- plantation model with the rate of megakaryocytic recovery for individual patients after autologous PBPC transplantation was evaluated. Engraftment into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) and NOD-SCID-β2mnull mice was compared for patients with rapid (11 days) PLT recovery (good engrafters, GEs) versus those with delayed (18 days) PLT engraftment (poor engrafters, PEs). PBPCs (1 × 106 CD34+ cells) were transplanted into sublethally irradiated (300 cGy) mice, and human WBC and human PLT engraftment were analyzed by FACS in the blood weekly. Human WBCs and human CFU-megakaryocytes (Mks) in the marrow were determined 6 to 7 weeks after transplant. Six PEs and five GEs were analyzed. Four of six PEs showed no human cell engraftment, whereas five of five GEs showed multilineage human hematopoiesis including the presence of CFU-Mks. Human WBC engraftment and human CFU-Mks differed significantly between GEs and PEs (p < 0.01). NOD-SCID-β2mnull had significantly higher levels of human engraftment than NOD-SCID mice (p < 0.05). The two PEs whose PBPCs were capable of engrafting in the mice had underlying liver abnormalities that may have played a role in their delayed engraftment. Time to PLT recovery in patients correlates strongly with human PLT and human WBC engraftment and with the number of human CFU-Mks (p < 0.05) in a xenogeneic transplant model. This model may be useful for future studies to test therapeutic strategies for enhancement of engraftment. [ABSTRACT FROM AUTHOR]