Evidence map›Paper›PMID 23197662›Full record

ArticleStem cells translational medicine2012

Apoptotic susceptibility to DNA damage of pluripotent stem cells facilitates pharmacologic purging of teratoma risk.

Alyson J Smith, Natalie G Nelson, Saji Oommen, Katherine A Hartjes, Clifford D Folmes, Andre Terzic, Timothy J Nelson

Open access · goldAbstract readValidation Study
In one paragraph

Article in Stem cells translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  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. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Tumor prevention facilitates delayed transplant of stem cell-derived motoneurons.Annals of clinical and translational neurology · 2016
    Article
  15. Review
  16. Stem cells: the pursuit of genomic stability.International journal of molecular sciences · 2014
    Review
  17. Metabolic regulation of redox status in stem cells.Antioxidants & redox signaling · 2014
    Review
  18. Article
  19. Review
  20. 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

7 authors at 4 institutions in 1 country.

Alyson J SmithDepartment of Medicine and Transplant Center, Mayo Clinic, Rochester, MN 55905, USA.
Natalie G Nelson
Saji Oommen
Katherine A Hartjes
Clifford D Folmes
Andre Terzic
Timothy J Nelson
Mayo Clinic · USMayo Clinic in Arizona · USMayo Clinic in Florida · USWinnMed · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Predoctoral Training Program in Molecular PharmacologyT32GM072474 · NIGMS · MAYO CLINIC ROCHESTER · PI KARNITZ, LARRY M · 2005 to 2020
$2.4M
Dysfunctional regeneration in cardiomyopathy: iPS-based diagnosis and therapyDP2OD007015 · OD · MAYO CLINIC ROCHESTER · PI NELSON, TIMOTHY JAMES · 2010 to 2010
$2.4M
NCI NIH HHS 5P30 CA15083-36NCI NIH HHS P30 CA015083NIGMS NIH HHS T32 GM072474NIH HHS DP2 OD007015
6 · The paper itself

Abstract

Pluripotent stem cells have been the focus of bioengineering efforts designed to generate regenerative products, yet harnessing therapeutic capacity while minimizing risk of dysregulated growth remains a challenge. The risk of residual undifferentiated stem cells within a differentiated progenitor population requires a targeted approach to eliminate contaminating cells prior to delivery. In this study we aimed to validate a toxicity strategy that could selectively purge pluripotent stem cells in response to DNA damage and avoid risk of uncontrolled cell growth upon transplantation. Compared with somatic cell types, embryonic stem cells and induced pluripotent stem cells displayed hypersensitivity to apoptotic induction by genotoxic agents. Notably, hypersensitivity in pluripotent stem cells was stage-specific and consistently lost upon in vitro differentiation, with the mean half-maximal inhibitory concentration increasing nearly 2 orders of magnitude with tissue specification. Quantitative polymerase chain reaction and Western blotting demonstrated that the innate response was mediated through upregulation of the BH3-only protein Puma in both natural and induced pluripotent stem cells. Pretreatment with genotoxic etoposide purged hypersensitive pluripotent stem cells to yield a progenitor population refractory to teratoma formation upon transplantation. Collectively, this study exploits a hypersensitive apoptotic response to DNA damage within pluripotent stem cells to decrease risk of dysregulated growth and augment the safety profile of transplant-ready, bioengineered progenitor cells.

Indexed as

ApoptosisDNA DamageAnimalsAnnexin A5Apoptosis Regulatory ProteinsBlotting, WesternCell DifferentiationCells, CulturedEmbryoid BodiesEmbryonic Stem CellsEtoposideFibroblastsFlow CytometryGenomic InstabilityInhibitory Concentration 50LentivirusAnnexin A5Apoptosis Regulatory ProteinsEtoposidePUMA protein, mouseRNA, Small InterferingTumor Suppressor Proteins

Identifiers

PMID23197662
PMCPMC3659660
OpenAlexW2170626923

What OpenQuestion holds

Textmetadata
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.