Biology subjects

Wissing, T. B.

Publications and source records attributed to Wissing, T. B..

3 recordsLinked to original sources

bioRxiv2023

The Effect of Mechanical Stimuli on the Phenotypic Plasticity of Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells in a 3D Hydrogel

IntroductionVascular smooth muscle cells (VSMCs) play a pivotal role in vascular homeostasis, with dysregulation leading to vascular complications. Human induced pluripotent stem cell (hiPSC)-derived VSMCs offer prospects for personalized disease modeling and regenerative strategies. Current research lacks comparative studies on the impact of 3D substrate properties under cyclic strain on phenotype adaptation in hiPSC-derived VSMCs. Here we investigated the potential of human mural cells derived from hiPSC-derived organoids (ODMCs) to undergo phenotypical adaptation under various biological and 3D mechanical stimuli. Methods and resultsODMCs were cultured in 2D conditions with synthetic or contractile differentiation medium, or 3D Gelatin Methacryloyl (GelMa) substrates with varying degrees of functionalization and percentages to modulate material stiffness, elasticity, and crosslink density. Cells in 3D substrates were exposed to cyclic unidirectional strain. Phenotype characterization was conducted using specific markers through immunofluorescence and gene expression analysis. Under static 2D culture, ODMCs derived from hiPSCs exhibited a VSMC phenotype, expressing key mural markers, and demonstrated a level of phenotypic plasticity like primary human vSMCs. In static 3D culture, higher substrate stiffness, lower elasticity and higher crosslink density promoted a contractile phenotype in ODMCs and vSMCs. Dynamic stimulation in 3D substrate promoted a switch towards a contractile phenotype in both cell types. ConclusionOur study demonstrates a phenotypic plasticity of human ODMCs in response to 2D biological and 3D mechanical stimuli that equals that of primary human vSMCs. These findings may contribute to the advancement of tailored approaches for vascular disease modelling and regenerative strategies

cell biology↗

bioRxiv2021

Tissue-engineered collagenous fibrous cap models to systematically elucidate atherosclerotic plaque rupture.

A significant amount of vascular thrombotic events is associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 x 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, a soft 2 mm O fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of an successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.

bioengineering↗

bioRxiv2019

Human in vitro model of material-driven vascular regeneration reveals how cyclic stretch and shear stress differentially modulate inflammation and tissue formation

1Resorbable synthetic scaffolds designed to regenerate living tissues and organs inside the body emerge as a clinically attractive technology to replace diseased blood vessels. However, mismatches between scaffold design and in vivo hemodynamic loading (i.e., cyclic stretch and shear stress) can result in aberrant inflammation and adverse tissue remodeling, leading to premature graft failure. Yet, the underlying mechanisms remain elusive. Here, a human in vitro model is presented that mimics the transient local inflammatory and biomechanical environments that drive scaffold-guided tissue regeneration. The model is based on the co-culture of human (myo)fibroblasts and macrophages in a bioreactor platform that decouples cyclic stretch and shear stress. Using a resorbable supramolecular elastomer as the scaffold material, it is revealed that cyclic stretch initially reduces pro-inflammatory cytokine secretion and, especially when combined with shear stress, stimulates IL-10 secretion. Moreover, cyclic stretch stimulates downstream (myo)fibroblast proliferation and neotissue formation. In turn, shear stress attenuates cyclic-stretch-induced tissue growth by enhancing MMP-1/TIMP-1-mediated collagen remodeling, and synergistically alters (myo)fibroblast phenotype when combined with cyclic stretch. The findings suggest that shear stress acts as a stabilizing factor in cyclic stretch-induced tissue formation and highlight the distinct roles of hemodynamic loads in the design of resorbable vascular grafts.

bioengineering↗