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Cited by 88Cardiac Valve Diseases and TreatmentsTissue Engineering and Regenerative MedicineMesenchymal stem cell research

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Modulation of Human Valve Interstitial Cell Phenotype and Function Using a Fibroblast Growth Factor 2 Formulation

Open access
Latif, Najma, Quillon, Alfred, Sarathchandra, Padmini, McCormack, Ann, Lozanoski, Alec, Yacoub, Magdi H., Chester, Adrian H.·2015·PLOS ONE
DOI 10.1371/journal.pone.0127844PMC PMC4456368
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Abstract

Valve interstitial cells (VICs) are fibroblastic in nature however in culture it is widely accepted that they differentiate into a myofibroblastic phenotype. This study assessed a fibroblast culture media formulation for its ability to maintain the phenotype and function of VICs as in the intact healthy valve. Normal human VICs were cultured separately in standard DMEM and in fibroblast media consisting of FGF2 (10 ng/ml), insulin (50 ng/ml) and 2% FCS for at least a week. Cell morphology, aspect ratio, size, levels and distribution of protein expression, proliferation, cell cycle, contraction and migration were assessed. Some VICs and some valve endothelial cells expressed FGF2 in valve tissue and this expression was increased in calcified valves. VICs in DMEM exhibited large, spread cells whereas VICs in fibroblast media were smaller, elongated and spindly. Aspect ratio and size were both significantly higher in DMEM (p<0.01). The level of expression of α-SMA was significantly reduced in fibroblast media at day 2 after isolation (p<0.01) and the expression of α-SMA, SM22 and EDA-fibronectin was significantly reduced in fibroblast media at days 7 and 12 post-isolation (p<0.01). Expression of cytoskeletal proteins, bone marker proteins and extracellular matrix proteins was reduced in fibroblast media. Proliferation of VICs in fibroblast media was significantly reduced at weeks 1 (p<0.05) and 2 (p<0.01). Collagen gel contraction was significantly reduced in fibroblast media (p<0.05). VICs were found to have significantly fewer and smaller focal adhesions in fibroblast media (p<0.01) with significantly fewer supermature focal adhesions in fibroblast media (p<0.001). Ultrastructurally, VICs in fibroblast media resembled native VICs from intact valves. VICs in fibroblast media demonstrated a slower migratory ability after wounding at 72 hours (p<0.01). Treatment of human VICs with this fibroblast media formulation has the ability to maintain and to dedifferentiate the VICs back to a fibroblastic phenotype with phenotypic and functional characteristics ascribed to cells in the intact valve. This methodology is fundamental in the study of normal valve biology, pathology and in the field of tissue engineering.

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  • Transition of VICs into myofibroblast-like cells is an early process in the development of CAVS.

    “Data have consistently shown that transition of VICs into myofibroblast-like cells was an early process in the development of CAVS (Latif et al., 2015; Schlotter et al., 2018; Taylor et al., 2000).”

    From Enhancer-associated aortic valve stenosis risk locus 1p21.2 alters NFATC2 binding site and promotes fibrogenesis (2021) · cites this paper as Latif et al., 2015

    The Introduction reports that VICs become reactivated to a myofibroblastic phenotype during valve sclerosis and stenosis. It does not establish that this transition occurs early in the development of calcific aortic valve stenosis; the rapid transition described in the Discussion occurs in culture, not during disease progression. (LLM, conf=0.85)

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Metadata

Authors
Latif, N., Quillon, A., Sarathchandra, P., McCormack, A., Lozanoski, A., Yacoub, M. H., & Chester, A. H.
Affiliations
  • Harefield Hospital (GB)
  • Lyon 1 Université (FR)
Corresponding author
Latif, Najma
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-06-04
Volume
10
Issue
6
Pages
e0127844
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0127844
PMC
PMC4456368
OpenAlex
W1521574455
Cited by
85
References
43
Citations by year
2026: 2 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 5 · 2017: 14 · 2016: 3
FWCI
5.34
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords
valvular interstitial cells, fibroblast growth factor 2, alpha-smooth muscle actin, focal adhesions, cell migration, cell proliferation, collagen gel contraction, valve calcification, extracellular matrix, endothelial cells, heart valve tissue engineering
MeSH terms
Actins, Adolescent, Adult, Aortic Valve, Cell Movement, Cells, Cultured, Child, Culture Media, Flow Cytometry, Humans, Middle Aged, Phenotype, Time Factors, Fibroblast Growth Factor 2, Focal Adhesions, Cell Proliferation, Young Adult, Interstitial Cells of Cajal

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