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Transfusion. 2004 Apr;44(4):555-66.

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

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  • 1Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520-8035, USA.

Abstract

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.

PMID:
15043572
[PubMed - indexed for MEDLINE]
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