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Isolation of Human Primary Valve Cells for In vitro Disease Modeling
Published on: April 16, 2021
Modeling calcific aortic valve disease with engineered human valve tissues identifies SAMHD1 as a therapeutic target
Xiangfu Meng1, Qian Zhou1, Zijin Zhu1
1Stem Cells and Tissue Engineering Manufacture Center, College of Life Sciences, Hubei University, Wuhan, 430062, China; National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei University, Wuhan, 430062, China.
Biomaterials
|July 25, 2026
Summary
Engineered heart valve tissues (EVTs) from human stem cells mimic calcific aortic valve disease (CAVD). A novel composite model revealed SAMHD1 as a key therapeutic target for CAVD, offering new treatment possibilities.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cardiovascular Research
Background:
- Valvular heart disease (VHD), particularly calcific aortic valve disease (CAVD), affects millions globally with no effective drug treatments.
- Current animal and cellular models for CAVD lack physiological relevance and scalability.
- There is a critical need for advanced in vitro models to study CAVD pathogenesis and develop therapies.
Purpose of the Study:
- To develop a novel engineered valvular tissue (EVT) model using human induced pluripotent stem cells (hiPSCs) to mimic CAVD.
- To create a biomechanically active composite tissue by integrating EVTs with hiPSC-derived cardiomyocytes.
- To identify and validate therapeutic targets for CAVD using this innovative model.
Main Methods:
- Fabrication of EVTs from hiPSC-derived valvular interstitial cells (VICs) within a 3D hydrogel system for anisotropic alignment.
- Assembly of EVTs with hiPSC-derived cardiomyocytes to create a self-stimulating composite tissue model.
- Induction of calcification in EVTs under static and dynamic mechanical loading, followed by transcriptomic analysis and pharmacological intervention.
Main Results:
- The EVT model accurately recapitulated key features of CAVD, including matrix remodeling, fibrosis, and hydroxyapatite deposition.
- The composite model demonstrated that mechanical stress significantly exacerbates valve calcification.
- Transcriptomic analysis identified SAMHD1 as a core regulator of CAVD, and its inhibition reduced calcification and improved tissue function.
Conclusions:
- Engineered valvular tissues (EVTs) provide a physiologically relevant and scalable model for studying calcific aortic valve disease (CAVD).
- The self-stimulating myocardium-valve composite model elucidates the role of mechanical stress in CAVD progression.
- SAMHD1 is validated as a promising therapeutic target for developing pharmacotherapies against CAVD.
Keywords:
Calcific aortic valve diseaseEngineered valvular tissueHuman induced pluripotent stem cellsMechanical stressMyocardium-valve integrated modelSAMHD1
