NDLI: Microdevice array-based identification of distinct mechanobiological response profiles in layer-specific valve interstitial cells

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Microdevice array-based identification of distinct mechanobiological response profiles in layer-specific valve interstitial cells

Content Provider	Royal Society of Chemistry (RSC)
Author	Likhitpanichkul, Morakot Sun, Yu Beca, Bogdan M. Lam, Cameron J. Simmons, Craig A. Moraes, Christopher
Copyright Year	2013
Abstract	Aortic valve homeostasis is mediated by valvular interstitial cells (VICs) found in spatially distinct and mechanically dynamic layers of the valve leaflet. Disease progression is associated with the pathological differentiation of VICs to myofibroblasts, but the mechanobiological response profiles of cells specific to different layers in the leaflet remains undefined. Conventional mechanically dynamic macroscale culture technologies require a large number of cells per set of environmental conditions. However, large scale expansion of primary VICs in vitro does not maintain in vivo phenotypes, and hence conventional macroscale techniques are not well-suited to systematically probe response of these cell types to combinatorially manipulated mechanobiological cues. To address this issue, we developed a microfabricated composite material screening array to determine the combined effects of dynamic substrate stretch, soluble cues and matrix proteins on small populations of primary cells. We applied this system to study VICs isolated from distinct layers of the valve leaflet and determined that (1) mechanical stability and cellular adhesion to the engineered composite materials were significantly improved as compared to conventional stretching technologies; (2) VICs demonstrate layer-specific mechanobiological profiles; and (3) mechanical stimulation, matrix proteins and soluble cues produce integrated and distinct responses in layer-specific VIC populations. Strikingly, myofibroblast differentiation was most significantly influenced by cell origin, despite the presence of potent mechanobiological cues such as applied strain and TGF-β1. These results demonstrate that spatially-distinct VIC subpopulations respond differentially to microenvironmental cues, with implications for valve tissue engineering and pathobiology. The developed platform enables rapid identification of biological phenomena arising from systematically manipulating the cellular microenvironment, and may be of utility in screening mechanosensitive cell cultures with applications in drug screening, tissue engineering and fundamental cell biology.
Starting Page	673
Ending Page	680
Page Count	8
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	5
Issue Number	4
Journal	Integrative Biology
DOI	10.1039/c3ib20254b
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Homeostasis Variable-length intake manifold Myofibroblast Microfabrication Composite material Extracellular matrix Tissue engineering Fundamental domain Molecular biology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

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