Key result
Culturing aortic valve cells and tissues in micro-physiological-systems with fluidic and hypoxic conditions significantly increased hypoxia-related gene expression and improved tissue viability.
Why the study?
Static 2D valvular interstitial cell cultures and animal models are limited in their ability to reflect human aortic valve calcification.
Does culturing aortic valve cells and tissues in micro-physiological-systems with pulsatile flow and hypoxia improve viability and reflect pathophysiological processes compared to static cultures?
Does culturing aortic valve cells and tissues in micro-physiological-systems with pulsatile flow and hypoxia improve viability and reflect pathophysiological processes compared to static cultures?
Micro-physiological systems with pulsatile flow and hypoxia regulation offer a viable alternative to static 2D cultures and animal models for studying aortic valve pathophysiology.
Supports MPS with hypoxia/flow for valve tissue models; leaves open human translation from animal data.
Aortic valve (AV) stenosis is characterized by tissue fibrosis and calcification. Fibrous thickening can result in reduced tissue oxygen supply leading to pathological valvular interstitial cell (VIC) differentiation and calcification. Static 2D VIC cultures and animal models are limited in the ability to reflect human AV calcification. Culturing of VICs in micro-physiological-systems (MPS) in a pulsatile flow and the establishment of a modular AV tissue incubation chamber (TIC) are new approaches to evaluate pathophysiological processes of AV disease. Therefore, a MPS able to adjust hypoxic conditions was applied for VIC culture. A significant increase of mRNA-expression of EGLN1 and HIF1α- regulated LDHA and HIF1α nuclear localisation were proven under hypoxia. AV tissue culture was established within a TIC and viability was monitored by Resazurin-reduction in the incubation medium and visualized by LDH-activity in tissue cryosections. Viability was compared between fluid and static incubated tissues revealing an advantageous effect of the fluidic assay condition. Consecutively, the application of MPS in AV research allows i) the investigation of VIC cultures with efficient oxygen regulation and ii) the culture of porcine or human AV tissues preserving viability and specifically reflecting in vivo parameters. These methods open up new possibilities beyond static 2D culture and facilitate a reduction of animal experiments in AV research.
No takes yet. Share an insight, caveat, or question.
Winkelkotte et al. (2021) studied Aortic valve stenosis. Micro-physiological-systems (MPS) and tissue incubation chamber (TIC) vs. Static 2D cultures and static incubated tissues was evaluated on Viability and mRNA-expression of EGLN1 and HIF1α-regulated LDHA. Culturing aortic valve cells and tissues in micro-physiological-systems with fluidic and hypoxic conditions significantly increased hypoxia-related gene expression and improved tissue viability.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: