期刊
BLOOD
卷 116, 期 2, 页码 193-200出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-02-271841
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资金
- Leukemia & Lymphoma Society
- Canadian Institutes for Health Research
- Stem Cell Network of Canadian National Centres of Excellence
- Canadian Cancer Society
- Terry Fox Foundation
- Genome Canada through the Ontario Genomics Institute, Ontario Institute for Cancer Research (province of Ontario)
- Canada Research Chair
- Ontario Ministry of Health and Long Term Care
The nonobese diabetic/severe combined immune deficiency (NOD-scid) xenotransplantation model is the gold standard for assaying human hematopoietic stem cell activity. Systematic advancements, such as depletion of natural killer cell activity with anti-CD122 antibody, direct intrafemoral injection, and deletion or truncation of IL2R gamma, have improved human cell engraftment; however, questions remain whether these mouse models are equivalent or, if not, which model is superior for assaying hematopoietic stem cell activity. To address this, we compared overall engraftment and multi-lineage differentiation of near-limiting doses of lineage-depleted human umbilical cord blood cells by direct intrafemoral injection into NOD/Lt-scid, NOD/Shi-scid, NOD/Lt-scid/IL2R gamma(null) (NSG), and NOD/Shi-scid/IL2R gamma(null) mice. Transplantation into NSG mice generated moderately higher human engraftment levels in bone marrow compared with other strains. At limiting doses, NSG mice of both sexes were 3.6-fold more sensitive in detecting SCID-repopulating cells compared with NOD/Lt-scid mice. However, NSG females exhibited higher engraftment at limiting cell doses, resulting in an overall increase in SCID-repopulating cell detection of 9-fold. Both NSG and NOD/Shi-scid/IL2R gamma(null) support significantly improved engraftment in peripheral tissues compared with NOD/Lt-scid and NOD/Shi-scid mice, whereas NSG mice provide greater human engraftment in bone marrow than all other strains, especially at limiting doses. (Blood. 2010; 116(2): 193-200)
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