Evidence map›Paper›PMID 30793529›Full record

ArticleStem cells translational medicine2019

Neutrophils Derived from Genetically Modified Human Induced Pluripotent Stem Cells Circulate and Phagocytose Bacteria In Vivo.

Lisa R Trump, Ramesh C Nayak, Abhishek K Singh, Sana Emberesh, Ashley M Wellendorf, Carolyn M Lutzko, Jose A Cancelas

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 56 citations in OpenAlex.

  1. CAR-engineered neutrophils derived from induced pluripotent stem cells: a new frontier in cellular immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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  3. Article
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  13. Article
  14. Neutrophils cultured ex vivo from CD34Journal of translational medicine · 2024
    Article
  15. Review
  16. Stem cells and pain.World journal of stem cells · 2023
    Review
  17. Modeling immunity in microphysiological systems.Experimental biology and medicine (Maywood, N.J.) · 2023
    Review
  18. iScience · 2023
    Article
  19. Article
  20. Review
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

7 authors at 1 institution in 1 country.

Lisa R TrumpDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Ramesh C NayakDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Abhishek K SinghDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Sana EmbereshDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Ashley M WellendorfDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Carolyn M LutzkoDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jose A CancelasDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.ORCID 0000-0002-1291-7233
Cincinnati Children's Hospital Medical Center · US

Funding

Cincinnati Center for Excellence in Molecular HematologyP30DK090971 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI ZHENG, YI · 2010 to 2015
$4.0M
G-CSF in Human Severe Congenital NeutropeniaR01GM110628 · NIGMS · CINCINNATI CHILDRENS HOSP MED CTR · PI CANCELAS, JOSE A., LUTZKO, CAROLYN M · 2015 to 2018
$1.2M
NIDDK NIH HHS P30 DK090971NIGMS NIH HHS R01 GM110628
6 · The paper itself

Abstract

Bacterial and fungal infections are a major cause of morbidity and mortality in neutropenic patients. Donor-derived neutrophil transfusions have been used for prophylaxis or treatment for infection in neutropenic patients. However, the short half-life and the limited availability of large numbers of donor-derived neutrophils for transfusion remain a significant hurdle in the implementation of neutrophil transfusion therapy. Here, we investigate the in vitro and in vivo activity of neutrophils generated from human induced pluripotent stem cells (iPSC), a potentially unlimited resource to produce neutrophils for transfusion. Phenotypic analysis of iPSC-derived neutrophils reveal reactive oxygen species production at similar or slightly higher than normal peripheral blood neutrophils, but have an ∼50%-70% reduced Escherichia coli phagocytosis and phorbol 12-myristate 13-acetate induced formation of neutrophil extracellular traps (NET). Signaling of granulocytic precursors identified impaired AKT activation, but not ERK or STAT3, in agonist-stimulated iPSC-derived neutrophils. Expression of a constitutively activated AKT in iPSC-derived neutrophils restores most phagocytic activity and NET formation. In a model of bacterial induced peritonitis in immunodeficient mice, iPSC-derived neutrophils, with or without corrected AKT activation, migrate similarly to the peritoneal fluid as peripheral blood neutrophils, whereas the expression of activated AKT significantly improves their phagocytic activity in vivo. Stem Cells Translational Medicine 2019;8:557-567.

Indexed as

PhagocytosisAdultAnimalsEscherichia coliExtracellular TrapsFemaleGranulocyte Colony-Stimulating FactorHumansInduced Pluripotent Stem CellsMaleMiceNeutrophilsPeritonitisProto-Oncogene Proteins c-aktReactive Oxygen SpeciesSignal TransductionGranulocyte Colony-Stimulating FactorProto-Oncogene Proteins c-aktReactive Oxygen SpeciesTetradecanoylphorbol AcetateAKTCirculationHuman induced pluripotent stem cellsNeutrophilsPhagocytosis

Identifiers

PMID30793529
PMCPMC6525559
OpenAlexW2916514471

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.