Contractions in hydrogels point to biochemical clues of valvular disorders

During aortic valve stenosis, valvular interstitial cells assume a persistently activated state that is normally transient and reserved for healing their microenvironments. While much work has shed light on the mechanical features of the disease, relatively little is known about the biochemical mechanisms, and nonsurgical interventions remain elusive. New work using hydrogels has provided clues for the mechanisms behind this disorder and future therapeutics.

Gonzalez Rodriguez et al. have demonstrated the use of a 3D hydrogel platform to determine how biochemical signals change valvular interstitial cell phenotype in a way that mimics native tissue. The group exposed porcine cells to different biochemical signals while growing cells within poly(ethylene glycol) hydrogels and assessing the effect on the cells’ phenotype, the set of traits marked by the expression of genes and presence of proteins.

The group’s findings mark one of the first uses of such hydrogels to study aberrant valvular interstitial cells in response to single and combined biochemical cues in 3D.

Cells exposed to TGF-β1 exhibited a disease-like phenotype, increasing gene expression related to matrix remodeling and α-SMA, a hallmark protein of stenotic structural changes in the valve. Functional contraction assays confirmed that exposure to TGF-β1 led to contraction of the hydrogels.

Cells treated with FGF-2 experienced a reduced diseaselike phenotype, including increased cellular proliferation, reduced contraction and decreased expression of α-SMA. The findings suggest that FGF-2 might have a reparative effect in valvular interstitial cell dysfunction.

The authors hope the paper will further stoke interest in both the role of FGF-2 in stenotic disorders and in 3D hydrogels as platforms to study the microenvironment surrounding cells, including more exploration into how 3D cell cultures respond to dynamic systems.

Source: “FGF-2 inhibits contractile properties of valvular interstitial cell myofibroblasts encapsulated in 3D MMP-degradable hydrogels,” by Andrea Gonzalez Rodriguez, Megan E. Schroeder, Cierra J. Walker, and Kristi S. Anseth, APL Bioengineering (2018). The article can be accessed at https://doi.org/10.1063/1.5042430 .