Evidence map›Paper›PMID 37964388›Full record

ArticleStem cell research & therapy2023

Bright ferritin for long-term MR imaging of human embryonic stem cells.

Keyu Zhuang, Rocco Romagnuolo, Tamilla Sadikov Valdman, Kyle D W Vollett, Daniel A Szulc, Hai-Ying Mary Cheng, Michael A Laflamme, Hai-Ling Margaret Cheng

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

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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

8 authors at 2 institutions in 2 countries.

Keyu ZhuangInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Rocco RomagnuoloMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Tamilla Sadikov ValdmanMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Kyle D W VollettInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Daniel A SzulcInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Hai-Ying Mary ChengDepartment of Biology, University of Toronto Mississauga, Mississauga, ON, Canada.
Michael A LaflammeMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Hai-Ling Margaret ChengInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada. hailing.cheng@utoronto.ca.ORCID 0000-0002-0733-9512
University of Toronto · CAUniversity Health Network · CA

Funding

Canada First Research Excellence Fund MbDC2-2019-01Canada First Research Excellence Fund MbDPEFR1-2021-04Canada Foundation for Innovation 34038Natural Sciences and Engineering Research Council of Canada RGPIN-2019-06137New Frontiers in Research Fund NFRFE-2020-00509
6 · The paper itself

Abstract

backgroundA non-invasive imaging technology that can monitor cell viability, retention, distribution, and interaction with host tissue after transplantation is needed for optimizing and translating stem cell-based therapies. Current cell imaging approaches are limited in sensitivity or specificity, or both, for in vivo cell tracking. The objective of this study was to apply a novel ferritin-based magnetic resonance imaging (MRI) platform to longitudinal tracking of human embryonic stem cells (hESCs) in vivo.

methodsHuman embryonic stem cells (hESCs) were genetically modified to stably overexpress ferritin using the CRISPR-Cas9 system. Cellular toxicity associated with ferritin overexpression and manganese (Mn) supplementation were assessed based on cell viability, proliferation, and metabolic activity. Ferritin-overexpressing hESCs were characterized based on stem cell pluripotency and cardiac-lineage differentiation capability. Cells were supplemented with Mn and imaged in vitro as cell pellets on a preclinical 3 T MR scanner. T1-weighted images and T1 relaxation times were analyzed to assess contrast. For in vivo study, three million cells were injected into the leg muscle of non-obese diabetic severe combined immunodeficiency (NOD SCID) mice. Mn was administrated subcutaneously. T1-weighted sequences and T1 mapping were used to image the animals for longitudinal in vivo cell tracking. Cell survival, proliferation, and teratoma formation were non-invasively monitored by MRI. Histological analysis was used to validate MRI results.

resultsFerritin-overexpressing hESCs labeled with 0.1 mM MnCl

conclusionsThe bright-ferritin platform provides the first demonstration of longitudinal cell tracking with signal recall, opening a window on the massive cell death that hESCs undergo in the weeks following transplantation before the surviving cell fraction proliferates to form teratomas.

Indexed as

Human Embryonic Stem CellsTeratomaAnimalsEmbryonic Stem CellsFerritinsHumansMagnetic Resonance ImagingMiceMice, SCIDFerritinsCell trackingFerritinHuman embryonic stem cellMolecular imagingReporter genes

Identifiers

PMID37964388
PMCPMC10647036
OpenAlexW4388656272

What OpenQuestion holds

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LicenceCC BY
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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.