The elastic properties of valve interstitial cells undergoing pathological differentiation

Wyss, Kristine; Yip, Cindy Ying Yin; Mirzaei, Zahra; Jin, Xiaofan; Chen, Jan-Hung; Simmons, Craig A.

doi:10.1016/j.jbiomech.2011.11.030

Cited by 58 publications

(52 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Myofibroblasts, which are found in large numbers in fibrotic body tissue and scars, are not just significantly stiffer than glial cells4344 but also highly contractile. The strain they apply on their environment leads to a stiffening of the tissue surrounding them45, thus likely contributing to the overall enhanced stiffness of the scars.…”

Section: Discussionmentioning

confidence: 99%

The soft mechanical signature of glial scars in the central nervous system

et al. 2017

View full text Add to dashboard Cite

Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

show abstract

Section: Discussionmentioning

confidence: 99%

The soft mechanical signature of glial scars in the central nervous system

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Expression of SMαA is often used as an indicator of VIC activation and can be employed to show the potential progression of VICs towards a calcific phenotype [29]. VIC expression of SMαA was shown for filter paper culture wells (Fig.…”

Section: Smαa Expression In Vicsmentioning

confidence: 99%

Multilayer three-dimensional filter paper constructs for the culture and analysis of aortic valvular interstitial cells

et al. 2015

View full text Add to dashboard Cite

Culturing aortic valvular interstitial cells in an environment that models the aortic valve is an essential step towards understanding the progression of calcific aortic valve disease. Here the adaption of a 3D stacked paper-based culture system is presented for analyzing valve cells in a thick collagen gel matrix. Filter paper layers, modeled after a 96-well plate design, were printed with a wax well-plate template and then seeded with valve cell and collagen mixtures that quickly gelled into 3D cultures. Stacking these layers permitted extensive customization of culture thickness and cell density profiles to model the full thickness of native valve tissue.

show abstract

“…Deposition of more collagen fibers results in a higher stiffness of the ECM, and the disorganization of new deposited collagen fibers leads to spatial variation of matrix mechanics [8,9]. In vivo studies showed that disorganized collagen deposition is a common phenomenon in different types of tissue.…”

Section: Introductionmentioning

confidence: 99%

Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization

Killaars

DelRio

et al. 2017

Biomaterials

View full text Add to dashboard Cite

Valvular interstitial cells (VICs) are key regulators of the heart valve’s extracellular matrix (ECM), and upon tissue damage, quiescent VIC fibroblasts become activated to myofibroblasts. As the behavior of VICs during disease progression and wound healing is different compared to healthy tissue, we hypothesized that the organization of the matrix mechanics, which results from depositing of collagen fibers, would affect VIC phenotypic transition. Specifically, we investigated how the subcellular organization of ECM mechanical properties affects subcellular localization of Yes-associated protein (YAP), an early marker of mechanotransduction, and α-smooth muscle actin (α-SMA), a myofibroblast marker, in VICs. Photo-tunable hydrogels were used to generate substrates with different moduli and to create organized and disorganized patterns of varying elastic moduli. When porcine VICs were cultured on these matrices, YAP and α-SMA activation were significantly increased on substrates with higher elastic modulus or a higher percentage of stiff regions. Moreover, VICs cultured on substrates with a spatially disorganized elasticity had smaller focal adhesions, less nuclear localized YAP, less α-SMA organization into stress fibers and higher proliferation compared to those cultured on substrates with a regular mechanical organization. Collectively, these results suggest that disorganized spatial variations in mechanics that appear during wound healing and fibrotic disease progression may influence the maintenance of the VIC fibroblast phenotype, causing more proliferation, ECM remodeling and matrix deposition.

show abstract

The elastic properties of valve interstitial cells undergoing pathological differentiation

Cited by 58 publications

References 31 publications

The soft mechanical signature of glial scars in the central nervous system

The soft mechanical signature of glial scars in the central nervous system

Multilayer three-dimensional filter paper constructs for the culture and analysis of aortic valvular interstitial cells

Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization

Contact Info

Product

Resources

About