Antifibrotic effect of cyclic strain on a human cardiac fibrosis-on-a-chip platform
2023
University Medical Center Utrecht, Utrecht, Netherlands
Most investigated mechanotransduction pathways in cardiac fibroblasts seem to ultimately have profibrotic effects, which leaves an important question in cardiac fibrosis research unanswered: how do cardiac fibroblasts stay quiescent in the ever-beating human heart? In this study, a human cardiac fibrosis-on-a-chip platform was developed and utilized to investigate if and how cyclic strain affects fibrogenic signalling. The pneumatically actuated platform can expose engineered tissues to controlled strain magnitudes of 0–25% – which covers the entire physiological and pathological strain range in the human heart – and to biochemical stimuli and enables high-throughput screening of multiple samples. Microtissues of human fetal cardiac fibroblasts (hfCF) embedded in gelatin methacryloyl (GelMA) were 3D-cultured on this platform and exposed to strain conditions which mimic the healthy human heart. The results provide evidence of an antifibrotic effect of the applied strain conditions on cardiac fibroblast behaviour, emphasizing the influence of biomechanical stimuli on the fibrogenic process and giving a detailed overview of the mechanosensitive pathways and genes involved, which can be used in the development of novel therapies against cardiac fibrosis.
Cyclic strain has antifibrotic effects on the human cardiac fibroblast transcriptome in a human cardiac fibrosis-on-a-chip platform
Jesper Hjortnaes, Ye Wang
Added on: 02-05-2024
[1] https://www.sciencedirect.com/science/article/pii/S1751616123003338?via%3Dihub
