Human stem and progenitor cells have been shown to engraft in the marrow and spleen of sublethally irradiated NOD/SCID, sCID, Bg Nude/XID, NOD/SCID r chain"""""""""""""""""""""""" (NSG) mice and in fetal organs xenografted in NOD/SCID (SCID/Hu) mice [1]. In some studies, optimal engraftment required administration of specific recombinant human growth factors [2]. Nevertheless, the demonstration of multilineage hematopoiesis in NOD/SCID mice transplanted with isolated human CD34+/CD38- """"""""stem"""""""" cells supports the notion that xenogeneic transplantation in immunodeficient mice may serve as a surrogate model for human transplantation. Given the importance of preclinical in vivo models, the purpose of Core E is to provide CCEH members as well as other UW and FHCRC investigators with the resources and expertise needed to execute xenografting studies in immune deficient mice. The majority of studies involve analysis of hematopoietic reconstituting ability or immune function of defined populations of cells from humans, non-human primates, and dogs. Protocols have also been developed for evaluating the teratoma generating potential of ESC and iPSC, as well as the engraftment and regenerative potential of their derived progeny. Specifically Core E provides: 1) age appropriate NOD/SCID mice through an in-house breeding program, 2) expert consultation on experimental design, 3) help with obtaining lACUC approval, and 4) assistance with and/or full responsibility for conditioning and injecting mice, as well as sampling tissues from live and euthanized animals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK056465-16
Application #
8698734
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109
Hay, Kevin A; Turtle, Cameron J (2018) CD19-specific chimeric antigen receptor-modified (CAR)-T cell therapy for the treatment of chronic lymphocytic leukemia in the ibrutinib era. Immunotherapy 10:251-254
Yeung, Cecilia C S; McElhone, Scott; Chen, Xue Yan et al. (2018) Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome. Mod Pathol 31:569-580
OhAinle, Molly; Helms, Louisa; Vermeire, Jolien et al. (2018) A virus-packageable CRISPR screen identifies host factors mediating interferon inhibition of HIV. Elife 7:
Sorror, Mohamed L; Gooley, Ted A; Maclean, Kirsteen H et al. (2018) Pre-transplant expressions of microRNAs, comorbidities, and post-transplant mortality. Bone Marrow Transplant :
Gauthier, Jordan; Turtle, Cameron J (2018) Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy. Curr Res Transl Med 66:50-52
Correnti, Colin E; Laszlo, George S; de van der Schueren, Willem J et al. (2018) Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation. Leukemia 32:1239-1243
Roesch, Ferdinand; OhAinle, Molly; Emerman, Michael (2018) A CRISPR screen for factors regulating SAMHD1 degradation identifies IFITMs as potent inhibitors of lentiviral particle delivery. Retrovirology 15:26
Gust, Juliane; Hay, Kevin A; Hanafi, Laïla-Aïcha et al. (2017) Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells. Cancer Discov 7:1404-1419
Hay, Kevin A; Hanafi, Laïla-Aïcha; Li, Daniel et al. (2017) Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood 130:2295-2306
Turtle, Cameron J; Hay, Kevin A; Hanafi, Laïla-Aïcha et al. (2017) Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib. J Clin Oncol 35:3010-3020

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