Evidence map›Paper›PMID 38197423›Full record

ArticleVeterinary pathology2024

Humanization with CD34-positive hematopoietic stem cells in NOG-EXL mice results in improved long-term survival and less severe myeloid cell hyperactivation phenotype relative to NSG-SGM3 mice.

Elinor Willis, Jillian Verrelle, Esha Banerjee, Charles-Antoine Assenmacher, James C Tarrant, Nicholas Skuli, Moriah L Jacobson, Donald M O'Rouke, Zev A Binder, Enrico Radaelli

Open access · hybridAbstract read
In one paragraph

Article in Veterinary pathology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Humanized immune system animal models and their recent applications.Animal models and experimental medicine · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Human Immune System Reconstitution in NOD/Shi-Life (Basel, Switzerland) · 2025
    Article
  9. Humanized mouse models in MDS.Cell death & disease · 2025
    Review
  10. Article
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Elinor WillisComparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
Jillian VerrelleComparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
Esha BanerjeeComparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
Charles-Antoine AssenmacherComparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.ORCID 0000-0003-0073-2730
James C TarrantGlaxoSmithKline, Collegeville, PA.
Nicholas SkuliStem Cell and Xenograft Core, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Moriah L JacobsonTaconic Biosciences, Inc., Rensselaer, NY.
Donald M O'RoukeDepartment of Neurosurgery, Perelman School of Medicine, GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Zev A BinderDepartment of Neurosurgery, Perelman School of Medicine, GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Enrico RadaelliComparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.ORCID 0000-0002-2885-0221
University of Pennsylvania · USGlaxoSmithKline (United States) · USTaconic (United States) · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Aperio VERSA Digital Slide Scanner, eSlide Manager Database, and Advanced Image Analysis SoftwareS10OD023465 · OD · UNIVERSITY OF PENNSYLVANIA · PI DURHAM, AMY CLEVELAND · 2018 to 2018
$329k
NCI NIH HHS P30 CA016520NIH HHS S10 OD023465
6 · The paper itself

Abstract

NSG-SGM3 and NOG-EXL mice combine severe immunodeficiency with transgenic expression of human myeloid stimulatory cytokines, resulting in marked expansion of myeloid populations upon humanization with CD34+ hematopoietic stem cells (HSCs). Humanized NSG-SGM3 mice typically develop a lethal macrophage activation syndrome and mast cell hyperplasia that limit their use in long-term studies (e.g., humanization followed by tumor xenotransplantation). It is currently unclear to what extent humanized NOG-EXL mice suffer from the same condition observed in humanized NSG-SGM3 mice. We compared the effects of human CD34+ HSC engraftment in these two strains in an orthotopic patient-derived glioblastoma model. NSG-SGM3 mice humanized in-house were compared to NOG-EXL mice humanized in-house and commercially available humanized NOG-EXL mice. Mice were euthanized at humane or study endpoints, and complete pathological assessments were performed. A semiquantitative multiparametric clinicopathological scoring system was developed to characterize chimeric myeloid cell hyperactivation (MCH) syndrome. NSG-SGM3 mice were euthanized at 16 weeks after humanization because of severe deterioration of clinical conditions. Humanized NOG-EXL mice survived to the study endpoint at 22 weeks after humanization and showed less-severe MCH phenotypes than NSG-SGM3 mice. Major differences included the lack of mast cell expansion and limited tissue/organ involvement in NOG-EXL mice compared to NSG-SGM3 mice. Engraftment of human lymphocytes, assessed by immunohistochemistry, was similar in the two strains. The longer survival and decreased MCH phenotype severity in NOG-EXL mice enabled their use in a tumor xenotransplantation study. The NOG-EXL model is better suited than the NSG-SGM3 model for immuno-oncology studies requiring long-term survival after humanization.

Indexed as

Antigens, CD34Hematopoietic Stem CellsHematopoietic Stem Cell TransplantationMice, TransgenicMyeloid CellsAnimalsDisease Models, AnimalHumansMicePhenotypeAntigens, CD34hemophagocytic lymphohistiocytosishuman hematopoietic stem cellshumanizationmacrophage activation syndromemast cell hyperplasiamouseNOG-EXLNSG-SGM3

Identifiers

PMID38197423
PMCPMC11264550
OpenAlexW4390702685

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.