Evidence map›Paper›PMID 39536761›Full record

ArticleCell stem cell2025

Post-transplant G-CSF impedes engraftment of gene-edited human hematopoietic stem cells by exacerbating p53-mediated DNA damage response.

Daisuke Araki, Vicky Chen, Neelam Redekar, Christi Salisbury-Ruf, Yan Luo, Poching Liu, Yuesheng Li, Richard H Smith, Pradeep Dagur, Christian Combs and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Daisuke ArakiCellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Vicky ChenIntegrated Data Science Services (IDSS), National Institutes of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
Neelam RedekarIntegrated Data Science Services (IDSS), National Institutes of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
Christi Salisbury-RufCellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Yan LuoDNA Sequencing and Genomics Core Facility, NHLBI, NIH, Bethesda, MD 20892, USA.
Poching LiuDNA Sequencing and Genomics Core Facility, NHLBI, NIH, Bethesda, MD 20892, USA.
Yuesheng LiDNA Sequencing and Genomics Core Facility, NHLBI, NIH, Bethesda, MD 20892, USA.
Richard H SmithCellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Pradeep DagurFlow Cytometry Core Facility, NHLBI, NIH, Bethesda, MD 20892, USA.
Christian CombsLight Microscopy Core Facility, NHLBI, NIH, Bethesda, MD 20892, USA.
Andre LarochelleCellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: larochea@nhlbi.nih.gov.

Funding

Regenerative Therapies for Inherited Blood Disorders-Gene therapyZIAHL006172 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LAROCHELLE, ANDRE · 2013 to 2025
$13.0M
Intramural NIH HHS Z99 HL999999Intramural NIH HHS ZIA HL006172
6 · The paper itself

Abstract

Granulocyte-colony-stimulating factor (G-CSF) is commonly used to accelerate recovery from neutropenia following chemotherapy and autologous transplantation of hematopoietic stem and progenitor cells (HSPCs) for malignant disorders. However, its utility after ex vivo gene therapy in human HSPCs remains unexplored. We show that administering G-CSF from day 1 to 14 post-transplant impedes engraftment of CRISPR-Cas9 gene-edited human HSPCs in murine xenograft models. G-CSF affects gene-edited HSPCs through a cell-intrinsic mechanism, causing proliferative stress and amplifying the early p53-mediated DNA damage response triggered by Cas9-mediated DNA double-strand breaks. This underscores a threshold mechanism where p53 activation must reach a critical level to impair cellular function. Transiently inhibiting p53 or delaying the initiation of G-CSF treatment to day 5 post-transplant attenuates its negative impact on gene-edited HSPCs. The potential for increased HSPC toxicity associated with post-transplant G-CSF administration in CRISPR-Cas9 autologous HSPC gene therapy warrants consideration in clinical trials.

Indexed as

DNA DamageGene EditingGranulocyte Colony-Stimulating FactorHematopoietic Stem CellsHematopoietic Stem Cell TransplantationTumor Suppressor Protein p53AnimalsCRISPR-Cas SystemsHumansMiceGranulocyte Colony-Stimulating FactorTumor Suppressor Protein p53apoptosiscell-cycle arrestCRISPR-Cas9DNA damage responseDNA double-stranded breaksG-CSFgene editinggranulocyte colony stimulating factorhematopoietic stem and progenitor cellsp53 pathway

Identifiers

PMID39536761
PMCPMC11698648

What OpenQuestion 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 OpenQuestion graph.