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Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2003-01-0082.
Submitted January 10, 2003
Accepted May 26, 2003
Distinct hematopoietic stem/progenitor cell populations are responsible for repopulating NOD/SCID mice versus nonhuman primates
Peter A Horn, Bobbie M Thomasson, Brent L Wood, Robert G Andrews, Julia C Morris, and Hans-Peter Kiem*
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA
* Corresponding author; email: hkiem{at}fhcrc.org.
The nonobese diabetic/severe combined immune-deficient (NOD/SCID) mouse xenotransplant assay is the most commonly used surrogate assay for the study of human candidate stem cells. In contrast to large animal and human studies, however, it is limited by the short life span of the recipients, the limited proliferative demand placed on the transplanted cells, and the inability to support differentiation into all hematopoietic lineages. In the present study, we directly compared hematopoietic repopulation in NOD/SCID mice with autologous reconstitution in the baboon, a well-established preclinical large animal model for stem cell transplantation. Baboon CD34-enriched marrow cells were retrovirally marked and infused into both the irradiated baboon and NOD/SCID mice. While the percentage of gene-marked cells was very high and remained stable in NOD/SCID mice up to 12 weeks, including secondary transplants, we observed a considerable decline and an overall significantly (10-fold) lower percentage of gene-marked cells in the baboons. In addition, clonal integration site analysis revealed common proviral vector integrants in NOD/SCID repopulating cells and in the baboon at 6 weeks but not at 6 months after transplantation. These results suggest that distinct hematopoietic stem/progenitor cells are responsible for hematopoietic reconstitution in NOD/SCID mice versus nonhuman primates.
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