Evidence map›Paper›PMID 24905804›Full record

ArticleJournal of cellular biochemistry2014

High-resolution molecular validation of self-renewal and spontaneous differentiation in clinical-grade adipose-tissue derived human mesenchymal stem cells.

Amel Dudakovic, Emily Camilleri, Scott M Riester, Eric A Lewallen, Sergiy Kvasha, Xiaoyue Chen, Darcie J Radel, Jarett M Anderson, Asha A Nair, Jared M Evans and 11 more

Open access · greenAbstract read
In one paragraph

Article in Journal of cellular biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Long noncoding RNA (lncRNA)Genes & diseases · 2023
    Review
  10. Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Human meniscus allograft augmentation by allogeneic mesenchymal stromal/stem cell injections.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022
    Article
  16. Article
  17. Article
  18. Article
  19. Genetic profiling of human bone marrow mesenchymal stromal cells afterFrontiers in bioengineering and biotechnology · 2022
    Article
  20. Review

50 more citing papers are in PubMed but not listed here.

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

21 authors at 6 institutions in 2 countries.

Amel DudakovicDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota.
Emily Camilleri
Scott M Riester
Eric A Lewallen
Sergiy Kvasha
Xiaoyue Chen
Darcie J Radel
Jarett M Anderson
Asha A Nair
Jared M Evans
Aaron J Krych
Jay Smith
David R Deyle
Janet L Stein
Gary S Stein
Hee-Jeong Im
Simon M Cool
Jennifer J Westendorf
Sanjeev Kakar
Allan B Dietz
Andre J van Wijnen
Mayo Clinic · USMayo Clinic in Florida · USNational University of Singapore · SGRush University Medical Center · USUniversity of Vermont · USUniversity of Vermont Medical Center · US

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
Runx2 and Axin2 Interactions During Bone FormationR01DE020194 · NIDCR · MAYO CLINIC ROCHESTER · PI WESTENDORF, JENNIFER J · 2010 to 2014
$2.1M
Cell Cycle Regulation of Histone Gene ExpressionR01CA139322 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STEIN, GARY S. · 2009 to 2013
$1.6M
Engineering Pluripotent Stem Cells to Treat Osteogenesis ImperfectaR03AR065753 · NIAMS · MAYO CLINIC ROCHESTER · PI DEYLE, DAVID R · 2014 to 2016
$239k
NCATS NIH HHS UL1 TR000135NCI NIH HHS R01 CA139322NIAMS NIH HHS R01 AR049069NIAMS NIH HHS R03 AR065753NIDCR NIH HHS R01 DE020194
6 · The paper itself

Abstract

Improving the effectiveness of adipose-tissue derived human mesenchymal stromal/stem cells (AMSCs) for skeletal therapies requires a detailed characterization of mechanisms supporting cell proliferation and multi-potency. We investigated the molecular phenotype of AMSCs that were either actively proliferating in platelet lysate or in a basal non-proliferative state. Flow cytometry combined with high-throughput RNA sequencing (RNASeq) and RT-qPCR analyses validate that AMSCs express classic mesenchymal cell surface markers (e.g., CD44, CD73/NT5E, CD90/THY1, and CD105/ENG). Expression of CD90 is selectively elevated at confluence. Self-renewing AMSCs express a standard cell cycle program that successively mediates DNA replication, chromatin packaging, cyto-architectural enlargement, and mitotic division. Confluent AMSCs preferentially express genes involved in extracellular matrix (ECM) formation and cellular communication. For example, cell cycle-related biomarkers (e.g., cyclins E2 and B2, transcription factor E2F1) and histone-related genes (e.g., H4, HINFP, NPAT) are elevated in proliferating AMSCs, while ECM genes are strongly upregulated (>10-fold) in quiescent AMSCs. AMSCs also express pluripotency genes (e.g., POU5F1, NANOG, KLF4) and early mesenchymal markers (e.g., NES, ACTA2) consistent with their multipotent phenotype. Strikingly, AMSCs modulate expression of WNT signaling components and switch production of WNT ligands (from WNT5A/WNT5B/WNT7B to WNT2/WNT2B), while upregulating WNT-related genes (WISP2, SFRP2, and SFRP4). Furthermore, post-proliferative AMSCs spontaneously express fibroblastic, osteogenic, chondrogenic, and adipogenic biomarkers when maintained in confluent cultures. Our findings validate the biological properties of self-renewing and multi-potent AMSCs by providing high-resolution quality control data that support their clinical versatility.

Indexed as

AdipogenesisAdipose TissueBase SequenceCell- and Tissue-Based TherapyCell CommunicationCell Cycle CheckpointsCell DifferentiationCell ProliferationChondrogenesisDNA ReplicationExtracellular MatrixFlow CytometryHigh-Throughput Nucleotide SequencingHumansImmunophenotypingKruppel-Like Factor 4KLF4 protein, humanKruppel-Like Factor 4Membrane ProteinsThy-1 AntigensACTA2ADH1BADIPOGENESISADIPOSE-TISSUE DERIVED STROMAL CELLSASPNCCNB2CCND1CD105CD44CD73CD90CELL CYCLECHI3L1CHONDROGENESISCYCLINE2F1E2F7E2F8ECM2ENGEXTRACELLULAR MATRIXFIBROBLASTFMODH19HINFPHIST1H3HHIST1H4AHIST2H4AHIST2H4BHISTONEKLF4LINEAGE-COMMITMENTMESENCHYMAL STEM CELLMULTIPOTENTNANOGNESNPATNT5EOCT4OGNOSTEOGENESISPLURIPOTENTPODNPOU5F1RARRES2SFRP2SFRP4THY1TNNT3WISP2WNT2WNT2AWNT5AWNT5BWNT7B

Identifiers

PMID24905804
PMCPMC4225070
OpenAlexW1886451513

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.