Evidence map›Paper›PMID 27959319›Full record

ArticleAging2016

Accumulation of spontaneous γH2AX foci in long-term cultured mesenchymal stromal cells.

Margarita Pustovalova, Anna Grekhova, Тatiana Astrelina, Viktoria Nikitina, Ekaterina Dobrovolskaya, Yulia Suchkova, Irina Kobzeva, Darya Usupzhanova, Natalia Vorobyeva, Aleksandr Samoylov and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 19% 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

15 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Aging of Liver in Its Different Diseases.International journal of molecular sciences · 2022
    Review
  6. Review
  7. Long-Term Persistence of Increased Number of γH2AXBulletin of experimental biology and medicine · 2021
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. 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

16 authors at 4 institutions in 3 countries.

Margarita PustovalovaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Anna GrekhovaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Тatiana AstrelinaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Viktoria NikitinaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Ekaterina DobrovolskayaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Yulia SuchkovaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Irina KobzevaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Darya UsupzhanovaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Natalia VorobyevaState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Aleksandr SamoylovState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Andrey BushmanovState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Ivan V OzerovState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Alex ZhavoronkovInsilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, MD 21218, USA.
Sergey LeonovLife Sciences Center, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141700, Russia.
Dmitry KlokovCanadian Nuclear Laboratories, Chalk River, ON K0J1P0, Canada.
Andreyan N OsipovState Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
Federal Medical-Biological Agency · RUState Scientific Center of the Russian Federation - Federal Medical Biophysical Center named after A.I. Burnazyan · RUMoscow Institute of Physics and Technology · RUCanadian Nuclear Laboratories · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Expansion of mesenchymal stromal/stem cells (MSCs) used in clinical practices may be associated with accumulation of genetic instability. Understanding temporal and mechanistic aspects of this process is important for improving stem cell therapy protocols. We used γH2AX foci as a marker of a genetic instability event and quantified it in MSCs that undergone various numbers of passage (3-22). We found that γH2AX foci numbers increased in cells of late passages, with a sharp increase at passage 16-18. By measuring in parallel foci of ATM phosphorylated at Ser-1981 and their co-localization with γaH2AX foci, along with differentiating cells into proliferating and resting by using a Ki67 marker, we conclude that the sharp increase in γH2AX foci numbers was ATM-independent and happened predominantly in proliferating cells. At the same time, gradual and moderate increase in γH2AX foci with passage number seen in both resting and proliferating cells may represent a slow, DNA double-strand break related component of the accumulation of genetic instability in MSCs. Our results provide important information on selecting appropriate passage numbers exceeding which would be associated with substantial risks to a patient-recipient, both with respect to therapeutic efficiency and side-effects related to potential neoplastic transformations due to genetic instability acquired by MSCs during expansion.

Indexed as

Genomic InstabilityAdultCell DifferentiationCell ProliferationCells, CulturedHistonesHumansMaleMesenchymal Stem CellsPhosphorylationH2AX protein, humanHistonescellular senescenceDNA double-strand breaksgenome instabilitylong-term cultivationmesenchymal stromal cellsreplicative senescenceγH2AX foci

Identifiers

PMID27959319
PMCPMC5270682
OpenAlexW2565449436

What OpenQuestion holds

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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.