Evidence map›Paper›PMID 24647085›Full record

ArticlePloS one2014

A new class of pluripotent stem cell cytotoxic small molecules.

Mark Richards, Chee Wee Phoon, Gwendoline Tze Wei Goh, Eng Khuan Seng, Xu Ming Guo, Cherine Mei Fong Tan, Woon-Khiong Chan, Joel Mun Kin Lee

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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Review
  5. Review
  6. Article
  7. Article
  8. Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells.Journal of experimental & clinical cancer research : CR · 2020
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. 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

8 authors at 4 institutions in 2 countries.

Mark RichardsSchool of Chemical & Life Sciences, Nanyang Polytechnic, Singapore.
Chee Wee PhoonSchool of Chemical & Life Sciences, Nanyang Polytechnic, Singapore.
Gwendoline Tze Wei GohSingapore Eye Research Institute, 11 Third Hospital Avenue, Singapore.
Eng Khuan SengSchool of Chemical & Life Sciences, Nanyang Polytechnic, Singapore.
Xu Ming GuoSchool of Chemical & Life Sciences, Nanyang Polytechnic, Singapore.
Cherine Mei Fong TanSchool of Chemical & Life Sciences, Nanyang Polytechnic, Singapore.
Woon-Khiong ChanDepartment of Biological Sciences, National University of Singapore, Singapore.
Joel Mun Kin LeeSchool of Chemical & Life Sciences, Nanyang Polytechnic, Singapore; Food & Human Nutrition Programme (Singapore), School of Agriculture, Food and Rural Development, Agriculture Building, Newcastle University, Newcastle upon Tyne, United Kingdom.
Nanyang Polytechnic · SGNational University of Singapore · SGNewcastle University · GBSingapore Eye Research Institute · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A major concern in Pluripotent Stem Cell (PSC)-derived cell replacement therapy is the risk of teratoma formation from contaminating undifferentiated cells. Removal of undifferentiated cells from differentiated cultures is an essential step before PSC-based cell therapies can be safely deployed in a clinical setting. We report a group of novel small molecules that are cytotoxic to PSCs. Our data indicates that these molecules are specific and potent in their activity allowing rapid eradication of undifferentiated cells. Experiments utilizing mixed PSC and primary human neuronal and cardiomyocyte cultures demonstrate that up to a 6-fold enrichment for specialized cells can be obtained without adversely affecting cell viability and function. Several structural variants were synthesized to identify key functional groups and to improve specificity and efficacy. Comparative microarray analysis and ensuing RNA knockdown studies revealed involvement of the PERK/ATF4/DDIT3 ER stress pathway. Surprisingly, cell death following ER stress induction was associated with a concomitant decrease in endogenous ROS levels in PSCs. Undifferentiated cells treated with these molecules preceding transplantation fail to form teratomas in SCID mice. Furthermore, these molecules remain non-toxic and non-teratogenic to zebrafish embryos suggesting that they may be safely used in vivo.

Indexed as

Activating Transcription Factor 4AnimalsCell DifferentiationCells, CulturedCell SurvivalCytotoxinseIF-2 KinaseEmbryo, NonmammalianEndoplasmic Reticulum StressGene Expression RegulationHumansMiceMice, SCIDMyocytes, CardiacNeuronsOrgan SpecificityActivating Transcription Factor 4Atf4 protein, mouseCytotoxinsDdit3 protein, mouseeIF-2 KinaseReactive Oxygen SpeciesRNA, Small InterferingSmall Molecule LibrariesTranscription Factor CHOP

Identifiers

PMID24647085
PMCPMC3960094
OpenAlexW1979027894

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.