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Phenotype Transformation of Aortic Valve Interstitial Cells Due to Applied Shear Stresses Within a Microfluidic Chip.
- Source :
-
Annals of biomedical engineering [Ann Biomed Eng] 2017 Oct; Vol. 45 (10), pp. 2269-2280. Date of Electronic Publication: 2017 Jun 15. - Publication Year :
- 2017
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Abstract
- Despite valvular heart diseases constituting a significant medical problem, the acquisition of information describing their pathophysiology remains difficult. Due to valvular size, role and location within the body, there is a need for in vitro systems that can recapitulate disease onset and progression. This study combines the development of an in vitro model and its application in the mechanical stimulation of valvular cell transformation. Specifically, porcine aortic valvular interstitial cells (PAVIC) were cultured on polydimethylsiloxane microfluidic devices with or without exposure to shear stresses. Mechanobiological responses of valvular interstitial cells were evaluated at shear stresses ranging from 0 to 4.26 dyn/cm <superscript>2</superscript> . When flow rates were higher than 0.78 dyn/cm <superscript>2</superscript> , cells elongated and aligned with the flow direction. In addition, we found that shear stress enhanced the formation of focal adhesions and up-regulated PAVIC transformation, assessed by increased expression of α-smooth muscle actin and transforming growth factor β. This study reveals a link between the action of shear forces, cell phenotype transformation and focal adhesion formation. This constitutes the first step towards the development of co-cultures (interstitial-endothelial cells) on organ-on-a-chip devices, which will enable studies of the signaling pathways regulating force-induced valvular degeneration in microtissues and potential discovery of valvular degeneration therapies.
- Subjects :
- Actins biosynthesis
Animals
Aortic Valve pathology
Aortic Valve physiopathology
Focal Adhesions metabolism
Focal Adhesions pathology
Heart Valve Diseases metabolism
Heart Valve Diseases pathology
Heart Valve Diseases physiopathology
Swine
Transforming Growth Factor beta biosynthesis
Aortic Valve metabolism
Lab-On-A-Chip Devices
Microfluidic Analytical Techniques
Shear Strength
Stress, Mechanical
Subjects
Details
- Language :
- English
- ISSN :
- 1573-9686
- Volume :
- 45
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Annals of biomedical engineering
- Publication Type :
- Academic Journal
- Accession number :
- 28620766
- Full Text :
- https://doi.org/10.1007/s10439-017-1871-z