Evidence map›Paper›PMID 41987334›Full record

ArticleStem cell research & therapy2026

Comparative analysis of NSG and NBSGW mice for preclinical evaluation of gene-modified human hematopoietic stem and progenitor cells.

Caroline Y Kuo, Sean Harrington, Beatriz Campo-Fernandez, Stacia K Wyman, Xiaomeng Wu, Ruixue Zhang, Alejandro Espinoza, Bruno J de Andrade Silva, Julie M Sanchez, Sorel Fitz-Gibbon and 4 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Caroline Y KuoDivision of Allergy and Immunology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Sean HarringtonFormerly of Genetix Biotherapeutics, Somerville, MA, USA.
Beatriz Campo-FernandezDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Stacia K WymanInnovative Genomics Institute, University of California, Berkeley, CA, USA.
Xiaomeng WuDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Ruixue ZhangDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Alejandro EspinozaDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Bruno J de Andrade SilvaDivision of Dermatology, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Julie M SanchezDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Sorel Fitz-GibbonDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Chin-Hong TsengDepartment of Medicine, School of Medicine, University of California, Los Angeles, CA, USA.
Matteo PellegriniDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Melissa BonnerFormerly of Genetix Biotherapeutics, Somerville, MA, USA.
Zulema RomeroDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. zulemar@g.ucla.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Humanized mouse models are essential for evaluating the engraftment capacity and genetic integrity of gene-modified hematopoietic stem and progenitor cells (HSPCs). Here, we compared two widely used xenotransplantation platforms, NSG and NBSGW mice, in the context of lentiviral vector (LVV) transduction and CRISPR/Cas9-mediated gene correction. HSPCs harboring high LVV copy numbers exhibited engraftment deficits in NSG mice that were not observed in NBSGW mice. This discrepancy highlights the potential for the NBSGW model to mask safety liabilities of LVV-modified products due to its higher overall levels of human chimerism. In contrast, CRISPR/Cas9 editing with a single-stranded oligodeoxynucleotide donor yielded comparable correction rates in both models, even across decreasing input cell doses, demonstrating that long-term repopulating hematopoietic stem cells (HSCs) retain equivalent engraftment capacity in each strain. Single-cell RNA-sequencing revealed distinct progenitor populations that were markedly under-represented in the NSG model but preserved in NBSGW recipients, emphasizing the greater capacity of NBSGW mice to better support multilineage human hematopoiesis. Together, these findings establish that both NSG and NBSGW mice are suitable for assessing long-term engraftment and gene modification outcomes in human HSPCs. However, the significantly higher percentage of human cell chimerism in the NBSGW model may obscure cell populations with engraftment deficits. Careful selection of in vivo models is therefore critical for rigorous preclinical evaluation of gene therapy products prior to clinical translation.

Indexed as

Hematopoietic Stem CellsHematopoietic Stem Cell TransplantationAnimalsCRISPR-Cas SystemsGenetic VectorsHumansLentivirusMiceMice, Inbred NODMice, SCIDTransplantation, HeterologousCRISPR/Cas9Hematopoietic stem and progenitor cells (HSPCs)Humanized mouse modelsLentiviral vector (LVV)Long-term engraftment

Identifiers

PMID41987334
PMCPMC13196111

What Socratic holds

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Registered trials

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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 Socratic graph.