Evidence map›Paper›PMID 25226590›Full record

ArticlePloS one2014

Bioluminescent imaging of genetically selected induced pluripotent stem cell-derived cardiomyocytes after transplantation into infarcted heart of syngeneic recipients.

Vera Lepperhof, Olga Polchynski, Klaus Kruttwig, Chantal Brüggemann, Klaus Neef, Florian Drey, Yunjie Zheng, Justus P Ackermann, Yeong-Hoon Choi, Thomas F Wunderlich and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Visualization of regenerating and repairing hearts.Clinical science (London, England : 1979) · 2022
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Genome editing in cardiovascular diseases.Nature reviews. Cardiology · 2017
    Review
  13. Article
  14. Molecular imaging of stem cells for the treatment of acute myocardial infarction.International journal of clinical and experimental medicine · 2015
    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

13 authors at 3 institutions in 1 country.

Vera LepperhofInstitute for Neurophysiology, Medical Faculty, University of Cologne, Cologne, Germany.
Olga PolchynskiInstitute for Neurophysiology, Medical Faculty, University of Cologne, Cologne, Germany.
Klaus KruttwigIn-vivo-NMR Laboratory, Max Planck Institute for Neurological Research, Cologne, Germany.
Chantal BrüggemannIn-vivo-NMR Laboratory, Max Planck Institute for Neurological Research, Cologne, Germany.
Klaus NeefDepartment of Cardiothoracic Surgery, Heart Center of the University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Florian DreyDepartment of Cardiothoracic Surgery, Heart Center of the University of Cologne, Cologne, Germany.
Yunjie ZhengInstitute for Neurophysiology, Medical Faculty, University of Cologne, Cologne, Germany.
Justus P AckermannMax Planck Institute for Metabolism Research and Institute for Genetics, Cologne, Germany.
Yeong-Hoon ChoiDepartment of Cardiothoracic Surgery, Heart Center of the University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Thomas F WunderlichCenter for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Max Planck Institute for Metabolism Research and Institute for Genetics, Cologne, Germany; Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
Mathias HoehnIn-vivo-NMR Laboratory, Max Planck Institute for Neurological Research, Cologne, Germany.
Jürgen HeschelerInstitute for Neurophysiology, Medical Faculty, University of Cologne, Cologne, Germany.
Tomo SarićInstitute for Neurophysiology, Medical Faculty, University of Cologne, Cologne, Germany.
University of Cologne · DEMax Planck Institute for Metabolism Research · DEUniversity Hospital Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cell loss after transplantation is a major limitation for cell replacement approaches in regenerative medicine. To assess the survival kinetics of induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) we generated transgenic murine iPSC lines which, in addition to CM-specific expression of puromycin N-acetyl-transferase and enhanced green fluorescent protein (EGFP), also constitutively express firefly luciferase (FLuc) for bioluminescence (BL) in vivo imaging. While undifferentiated iPSC lines generated by random integration of the transgene into the genome retained stable FLuc activity over many passages, the BL signal intensity was strongly decreased in purified iPS-CM compared to undifferentiated iPSC. Targeted integration of FLuc-expression cassette into the ROSA26 genomic locus using zinc finger nuclease (ZFN) technology strongly reduced transgene silencing in iPS-CM, leading to a several-fold higher BL compared to iPS-CM expressing FLuc from random genomic loci. To investigate the survival kinetics of iPS-CM in vivo, purified CM obtained from iPSC lines expressing FLuc from a random or the ROSA26 locus were transplanted into cryoinfarcted hearts of syngeneic mice. Engraftment of viable cells was monitored by BL imaging over 4 weeks. Transplanted iPS-CM were poorly retained in the myocardium independently of the cell line used. However, up to 8% of cells survived for 28 days at the site of injection, which was confirmed by immunohistological detection of EGFP-positive iPS-CM in the host tissue. Transplantation of iPS-CM did not affect the scar formation or capillary density in the periinfarct region of host myocardium. This report is the first to determine the survival kinetics of drug-selected iPS-CM in the infarcted heart using BL imaging and demonstrates that transgene silencing in the course of iPSC differentiation can be greatly reduced by employing genome editing technology. FLuc-expressing iPS-CM generated in this study will enable further studies to reduce their loss, increase long-term survival and functional integration upon transplantation.

Indexed as

Molecular ImagingAnimalsCell DifferentiationCell LineGene ExpressionGene SilencingGenes, ReporterGenetic LociInduced Pluripotent Stem CellsLuminescent MeasurementsMaleMiceMyocardial InfarctionMyocytes, CardiacPromoter Regions, GeneticRNA, UntranslatedGt(ROSA)26Sor non-coding RNA, mouseRNA, Untranslated

Identifiers

PMID25226590
PMCPMC4167328
OpenAlexW2093833688

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.