TY - JOUR
T1 - A preclinical xenotransplantation animal model to assess human hematopoietic stem cell engraftment
AU - Angelopoulou, Maria K.
AU - Rinder, Henry
AU - Wang, Chao
AU - Burtness, Barbara
AU - Cooper, Dennis L.
AU - Krause, Diane S.
PY - 2004/4
Y1 - 2004/4
N2 - BACKGROUND: 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. STUDY DESIGN AND METHODS: The correlation between human cell engraftment in a mouse xenotransplantation 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. RESULTS: 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. CONCLUSIONS: 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.
AB - BACKGROUND: 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. STUDY DESIGN AND METHODS: The correlation between human cell engraftment in a mouse xenotransplantation 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. RESULTS: 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. CONCLUSIONS: 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.
UR - https://www.scopus.com/pages/publications/1842510507
UR - https://www.scopus.com/pages/publications/1842510507#tab=citedBy
U2 - 10.1111/j.1537-2995.2004.03285.x
DO - 10.1111/j.1537-2995.2004.03285.x
M3 - Article
C2 - 15043572
SN - 0041-1132
VL - 44
SP - 555
EP - 566
JO - Transfusion
JF - Transfusion
IS - 4
ER -