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

Transfusion. 2004 Apr;44(4):555-66. doi: 10.1111/j.1537-2995.2004.03285.x.


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-beta2m null 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 x 10(6) 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-beta2m null 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Graft Survival*
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Kinetics
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Animal*
  • Platelet Count
  • Predictive Value of Tests
  • Prognosis
  • Thrombopoiesis
  • Transplantation, Autologous
  • Transplantation, Heterologous