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Comparison of human cord blood engraftment between immunocompromised mouse strains
Open accessAbstract
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 IL2Rγ, 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 multilineage 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/IL2Rγnull (NSG), and NOD/Shi-scid/IL2Rγnull 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/IL2Rγnull 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.
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“As expected for this time point (Goyama et al., 2015; McDermott et al., 2010), engrafted human HSPCs gave rise mainly to B- and myeloid cells in the bone marrow in both Cas9 only and Cas9/hCD45-sg1 RNP engrafted mice, with no differences between Gundry et al.”
BackgroundAttenuation of miR-126 Activity Expands HSC In Vivo without Exhaustion
Lechman, E. R., Gentner, B., van Galen, P., Giustacchini, A., Saini, M., Boccalatte, F. E., Hiramatsu, H., Restuccia, U., Bachi, A., Voisin, V., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.09.001 · Cited by 208
Self-citationGene correction for SCID-X1 in long-term hematopoietic stem cells
Pavel-Dinu, M., Wiebking, V., Dejene, B. T., Srifa, W., Mantri, S., Nicolas, C. E., Lee, C., Bao, G., Kildebeck, E. J., Punjya, N., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09614-y · Cited by 167
Humanized bone marrow mouse model as a preclinical tool to assess therapy-mediated hematotoxicity
Cai, S., Wang, H., Bailey, B., Ernstberger, A., Juliar, B. E., Sinn, A. L., Chan, R. J., Jones, D. R., Mayo, L. D., Baluyut, A. R., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1959 · Cited by 32
Metadata
- Authors
- McDermott, S. P., Eppert, K., Lechman, E. R., Doedens, M., & Dick, J. E.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-07-15
- Volume
- 116
- Issue
- 2
- Pages
- 193-200
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2033548186
- Cited by
- 284
- References
- 0
- FWCI
- 15.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
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