Evidence map›Paper›PMID 26380983›Full record

ArticlePloS one2015

Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro.

Andreas Matthäus Bader, Kristin Klose, Karen Bieback, Dirk Korinth, Maria Schneider, Martina Seifert, Yeong-Hoon Choi, Andreas Kurtz, Volkmar Falk, Christof Stamm

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Extracellular vesicles: emerging therapeutic agents for liver fibrosis.Extracellular vesicles and circulating nucleic acids · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  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

10 authors at 4 institutions in 1 country.

Andreas Matthäus BaderBerlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany; Deutsches Herzzentrum Berlin, Berlin, Germany.
Kristin KloseBerlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Karen BiebackInstitute of Transfusion Medicine and Immunology, Ruprecht-Karls University of Heidelberg, Mannheim, Germany.
Dirk KorinthLabor Berlin GmbH, Berlin, Germany.
Maria SchneiderBerlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Martina SeifertBerlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Yeong-Hoon ChoiHeart Center, University of Cologne, Cologne, Germany.
Andreas KurtzBerlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Volkmar FalkDeutsches Herzzentrum Berlin, Berlin, Germany.
Christof StammBerlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany; Deutsches Herzzentrum Berlin, Berlin, Germany.
Charité - Universitätsmedizin Berlin · DEDeutsches Herzzentrum der Charité · DEHeidelberg University · DEUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone marrow-derived multipotent mesenchymal stromal cells (MSCs) upon transplantation in ischemic tissue. Given the interest in clinical applications of umbilical cord blood-derived MSCs, we developed a specific hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro by subjecting them to hypoxia and nutrient deprivation with or without preceding hypoxic preconditioning. Cell number, metabolic activity, surface marker expression, chromosomal stability, apoptosis (caspases-3/7 activity) and necrosis were determined, and phosphorylation, mRNA expression and protein secretion of selected apoptosis and angiogenesis-regulating factors were quantified. Then, human umbilical vein endothelial cells (HUVEC) were subjected to simulated ischemia in co-culture with hypoxically preconditioned or naïve cord blood MSCs, and HUVEC proliferation was measured. Migration, proliferation and nitric oxide production of HUVECs were determined in presence of cord blood MSC-conditioned medium. Cord blood MSCs proved least sensitive to simulated ischemia when they were preconditioned for 24 h, while their basic behavior, immunophenotype and karyotype in culture remained unchanged. Here, "post-ischemic" cell number and metabolic activity were enhanced and caspase-3/7 activity and lactate dehydrogenase release were reduced as compared to non-preconditioned cells. Phosphorylation of AKT and BAD, mRNA expression of BCL-XL, BAG1 and VEGF, and VEGF protein secretion were higher in preconditioned cells. Hypoxically preconditioned cord blood MSCs enhanced HUVEC proliferation and migration, while nitric oxide production remained unchanged. We conclude that hypoxic preconditioning protects cord blood MSCs by activation of anti-apoptotic signaling mechanisms and enhances their angiogenic potential. Hence, hypoxic preconditioning might be a translationally relevant strategy to increase the tolerance of cord blood MSCs to ischemia and improve their therapeutic efficacy in clinical applications.

Indexed as

ApoptosisBiomarkersCaspase 3Caspase 7Cell HypoxiaCell ProliferationCell SurvivalCoculture TechniquesFetal BloodHumansIschemic PreconditioningMesenchymal Stem CellsNeovascularization, PhysiologicBiomarkersCaspase 3Caspase 7

Identifiers

PMID26380983
PMCPMC4575058
OpenAlexW2202620261

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.