0000000000620618
AUTHOR
Barbara Goecke
Monocytes derived from humanized neonatal NOD/SCID/IL2Rγ(null) mice are phenotypically immature and exhibit functional impairments.
Trials of immune-modulating drugs in septic patients have mostly failed to demonstrate clinical efficacy. Thus, we sought to generate a surrogate model of myelomonocytic lineage differentiation that would potentially allow sepsis induction and preclinical testing of anti-inflammatory drugs. Comparing transplantation of cord blood-derived stem cells in neonatal NOD/SCID/IL2Rγ(null) (neonatal huNSG) mice with transplantation of adult peripheral mobilized stem cells into adult NSG (adult huNSG) recipients, we demonstrate that myelomonocytic lineage differentiation in neonatal huNSG mice is retarded and monocytes are phenotypically immature with respect to HLA-DR expression and the emergence of…
Engraftment of low numbers of pediatric acute lymphoid and myeloid leukemias into NOD/SCID/IL2Rcγnull mice reflects individual leukemogenecity and highly correlates with clinical outcome
Although immortalized cell lines have been extensively used to optimize treatment strategies in cancer, the usefulness of such in vitro systems to recapitulate primary disease is limited. Therefore, the design of in vivo models ideally utilizing patient-derived material is of critical importance. In this regard, NOD.Cg-Prkdc(scid) IL2rg(tmWjl) /Sz (NSG) mice have been reported to provide superior engraftment rates. However, limited data exist on the validity of such a model to constitute a surrogate marker for clinical parameters. We studied primary and serial engraftment on more than 200 NSG mice with 54 primary pediatric B cell precursor acute lymphatic leukemia (B-ALL), myeloid leukemia …
Long-Term Human CD34+ Stem Cell-Engrafted Nonobese Diabetic/SCID/IL-2Rγnull Mice Show Impaired CD8+ T Cell Maintenance and a Functional Arrest of Immature NK Cells
Abstract Allogeneic hematopoietic stem cell transplantation represents the most effective form of immunotherapy for chemorefractory diseases. However, animal models have been missing that allow evaluation of donor-patient–specific graft-versus-leukemia effects. Thus, we sought to establish a patient-tailored humanized mouse model that would result in long-term engraftment of various lymphocytic lineages and would serve as a donor-specific surrogate. Following transfer of donor-derived peripheral blood stem cells into NOD/SCID/IL-2Rγnull (NSG) mice with supplementation of human IL-7, we could demonstrate robust engraftment and multilineage differentiation comparable to earlier studies using …