Evidence map›Paper›PMID 26484394›Full record

ArticleGene2016

Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells.

Ling Ling, Emily T Camilleri, Torben Helledie, Rebekah M Samsonraj, Drew M Titmarsh, Ren Jie Chua, Oliver Dreesen, Christian Dombrowski, David A Rider, Mario Galindo and 6 more

Open access · greenAbstract read
In one paragraph

Article in Gene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 10% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  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

16 authors at 6 institutions in 3 countries.

Ling LingInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Emily T CamilleriDepartment of Orthopedic Surgery & Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Torben HelledieInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Rebekah M SamsonrajInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore; Department of Orthopedic Surgery & Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Drew M TitmarshInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Ren Jie ChuaInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Oliver DreesenInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Christian DombrowskiInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
David A RiderInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Mario GalindoMillennium Institute on Immunology and Immunotherapy, University of Chile, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70061, Correo 7, Santiago, Chile.
Ian LeeInstitute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore.
Wanjin HongInstitute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore.
James H HuiDepartment of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore.
Victor NurcombeInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
Andre J van WijnenDepartment of Orthopedic Surgery & Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: vanwijnen.andre@mayo.edu.
Simon M CoolInstitute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore. Electronic address: simon.cool@imb.a-star.edu.sg.
Agency for Science, Technology and Research · SGInstitute of Molecular and Cell Biology · SGMayo Clinic · USMayo Clinic in Arizona · USMillennium Institute on Immunology and Immunotherapy · CLNational University of Singapore · SG

Funding

Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
NIAMS NIH HHS AR49069NIAMS NIH HHS R01 AR049069
6 · The paper itself

Abstract

Chronic use of heparin as an anti-coagulant for the treatment of thrombosis or embolism invokes many adverse systemic events including thrombocytopenia, vascular reactions and osteoporosis. Here, we addressed whether adverse effects might also be directed to mesenchymal stem cells that reside in the bone marrow compartment. Harvested human bone marrow-derived mesenchymal stem cells (hMSCs) were exposed to varying doses of heparin and their responses profiled. At low doses (<200 ng/ml), serial passaging with heparin exerted a variable effect on hMSC proliferation and multipotentiality across multiple donors, while at higher doses (≥ 100 μg/ml), heparin supplementation inhibited cell growth and increased both senescence and cell size. Gene expression profiling using cDNA arrays and RNA-seq analysis revealed pleiotropic effects of low-dose heparin on signaling pathways essential to hMSC growth and differentiation (including the TGFβ/BMP superfamily, FGFs, and Wnts). Cells serially passaged in low-dose heparin possess a donor-dependent gene signature that reflects their altered phenotype. Our data indicate that heparin supplementation during the culturing of hMSCs can alter their biological properties, even at low doses. This warrants caution in the application of heparin as a culture supplement for the ex vivo expansion of hMSCs. It also highlights the need for careful evaluation of the bone marrow compartment in patients receiving chronic heparin treatment.

Indexed as

Bone Marrow CellsCell DifferentiationCell ProliferationCells, CulturedCulture MediaDose-Response Relationship, DrugGene Expression RegulationHeparinHumansMesenchymal Stem CellsSignal TransductionCulture MediaHeparinCell proliferationGlycosaminoglycansMesenchymal stem cellsMicroarrayMultipotency

Identifiers

PMID26484394
PMCPMC5330685
OpenAlexW2096941810

What OpenQuestion holds

Textmetadata
LicenceTDM
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.