NOD/SCID repopulating cells contribute only to short-term repopulation in the baboon.
We have previously compared the repopulation ability of gene-modified baboon CD34+ cells in an autologous transplantation versus a xenotransplant model in irradiated nonobese diabetic/severe combined immune deficiency (NOD/SCID) mice. Baboon CD34-selected marrow cells were transduced with a gammaretrovirus vector and infused into irradiated baboons and NOD/SCID mice. A limited integration-site analysis could only detect two common retrovirus integration sites in the NOD/SCID and monkey. Here, we performed locus-specific PCR on 30 clones recovered from NOD/SCID beta2-microglobulin mice reconstituted with transduced baboon CD34+ cells. We identified five common integrants in the baboon early after transplant (2-6 weeks) but none during the long-term follow-up (6 and 12 months). These results confirm that repopulating cells in the NOD/SCID mouse contribute only to short-term repopulation in a clinically relevant large animal model.
Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109-1024, USA.
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Mezquita
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Beard
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Kiem
D000818:Animals; D018952:Antigens, CD34; D002455:Cell Division; D002999:Clone Cells; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D017988:Gammaretrovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods* / Q000662:veterinary; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D010215:Papio; D016133:Polymerase Chain Reaction / Q000379:methods; D013995:Time; D014161:Transduction, Genetic / Q000379:methods; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D017931:DNA Primers