Evidence map›Paper›PMID 32449039›Full record

ArticleTissue engineering and regenerative medicine2020

Proangiogenic Hypoxia-Mimicking Agents Attenuate Osteogenic Potential of Adipose Stem/Stromal Cells.

Ahmed G Abu-Shahba, Arjen Gebraad, Sippy Kaur, Riku O Paananen, Hilkka Peltoniemi, Riitta Seppänen-Kaijansinkko, Bettina Mannerström

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Tissue engineering and regenerative medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 24% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Advances in Anti-Cancer Activities of Flavonoids inInternational journal of molecular sciences · 2022
    Review
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 1 institution in 2 countries.

Ahmed G Abu-ShahbaDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, PO Box 63, 00014, Helsinki, Finland. ahmed.abushahba@helsinki.fi.ORCID 0000-0003-2298-9828
Arjen GebraadDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, PO Box 63, 00014, Helsinki, Finland.ORCID 0000-0001-5774-237X
Sippy KaurDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, PO Box 63, 00014, Helsinki, Finland.ORCID 0000-0002-4371-1959
Riku O PaananenHelsinki Eye Lab, Ophthalmology, University of Helsinki and Helsinki University Hospital, Yliopistonkatu 4, 00100, Helsinki, Finland.
Hilkka PeltoniemiLaser Tilkka Ltd, Mannerheimintie 164, 2. krs, Helsinki, 00300, Finland.
Riitta Seppänen-KaijansinkkoDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, PO Box 63, 00014, Helsinki, Finland.ORCID 0000-0001-5348-7121
Bettina MannerströmDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, PO Box 63, 00014, Helsinki, Finland.ORCID 0000-0001-9316-5581
University of Helsinki · FI

Funding

Helsingin ja Uudenmaan Sairaanhoitopiiri TYH2016130Helsingin ja Uudenmaan Sairaanhoitopiiri Y1014SUL05Helsingin Yliopisto WBS490302Helsingin Yliopisto WBS73714112Ministry of Higher Education, Egypt 290243/2014-2015
6 · The paper itself

Abstract

backgroundInsufficient vascularization hampers bone tissue engineering strategies for reconstructing large bone defects. Delivery of prolyl-hydroxylase inhibitors (PHIs) is an interesting approach to upregulate vascular endothelial growth factor (VEGF) by mimicking hypoxic stabilization of hypoxia-inducible factor-1alpha (HIF-1α). This study assessed two PHIs: dimethyloxalylglycine (DMOG) and baicalein for their effects on human adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs).

methodsIsolated AT-MSCs were characterized and treated with PHIs to assess the cellular proliferation response. Immunostaining and western-blots served to verify the HIF-1α stabilization response. The optimized concentrations for long-term treatment were tested for their effects on the cell cycle, apoptosis, cytokine secretion, and osteogenic differentiation of AT-MSCs. Gene expression levels were evaluated for alkaline phosphatase (ALPL), bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor A (VEGFA), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). In addition, stemness-related genes Kruppel-like factor 4 (KLF4), Nanog homeobox (NANOG), and octamer-binding transcription factor 4 (OCT4) were assessed.

resultsPHIs stabilized HIF-1α in a dose-dependent manner and showed evident dose- and time dependent antiproliferative effects. With doses maintaining proliferation, DMOG and baicalein diminished the effect of osteogenic induction on the expression of RUNX2, ALPL, and COL1A1, and suppressed the formation of mineralized matrix. Suppressed osteogenic response of AT-MSCs was accompanied by an upregulation of stemness-related genes.

conclusionPHIs significantly reduced the osteogenic differentiation of AT-MSCs and rather upregulated stemness-related genes. PHIs proangiogenic potential should be weighed against their longterm direct inhibitory effects on the osteogenic differentiation of AT-MSCs.

Indexed as

OsteogenesisVascular Endothelial Growth Factor AAdipose TissueCell HypoxiaCollagen Type I, alpha 1 ChainHumansKruppel-Like Factor 4Stromal CellsCOL1A1 protein, humanCollagen Type I, alpha 1 ChainKLF4 protein, humanKruppel-Like Factor 4Vascular Endothelial Growth Factor AAdipose tissue-derived mesenchymal stem/stromal cellsBaicaleinDimethyloxalylglycineHypoxia-inducible factor-1alphaOsteogenesis

Identifiers

PMID32449039
PMCPMC7392999
OpenAlexW3027174440

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.