Distinct hematopoietic stem/progenitor cell populations are responsible for repopulating NOD/SCID mice compared with nonhuman primates.
The nonobese diabetic/severe combined immune-deficient (NOD/SCID) mouse xenotransplantation 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 the irradiated baboon and the NOD/SCID mice. Although the percentage of gene-marked cells was high and remained stable in NOD/SCID mice up to 12 weeks and in those that underwent secondary transplantation, we observed a considerable decline and overall a 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 compared with nonhuman primates.
Horn
Peter A
PA
Fred Hutchinson Cancer Research Center, D1-100, PO Box 19024, 1100 Fairview Ave N, Seattle, WA 98109-1024, USA.
Thomasson
Bobbie M
BM
Wood
Brent L
BL
Andrews
Robert G
RG
Morris
Julia C
JC
Kiem
Hans-Peter
HP
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D005822:Genetic Vectors; D006085:Graft Survival; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification* / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D016513:Mice, SCID / Q000502:physiology*; D010215:Papio / Q000502:physiology*; D011828:Radiation Chimera; D013045:Species Specificity; D014182:Transplantation, Autologous; D016662:Virus Integration
D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins