Functional vascular endothelium derived from human induced pluripotent stem cells

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Endothelial Cell Biology

Background:

• Vascular endothelium exhibits critical phenotypic plasticity crucial for vascular function.
• Dysregulated endothelial plasticity contributes to various human diseases.
• Studying human endothelium is hindered by the lack of patient-specific endothelial cells.

Purpose of the Study:

• To establish a human induced pluripotent stem cell (iPSC)-based cellular platform for studying endothelial biology.
• To investigate the functional phenotypic plasticity of iPSC-derived vascular endothelium.
• To assess the utility of iPSC-derived endothelium in cell-based assays for inflammatory and cardiovascular diseases.

Main Methods:

• Generation of vascular endothelium from human induced pluripotent stem cells (iPSCs).
• Assessment of endothelial cell responses to proinflammatory stimuli.
• Evaluation of endothelial barrier properties and responses to permeability factors.
• Induction of atheroprotective or atheroprone phenotypes using biomechanical or pharmacological stimuli.

Main Results:

• iPSC-derived endothelium demonstrated rich functional phenotypic plasticity, mirroring mature primary endothelial cells.
• These cells responded to inflammatory stimuli by expressing adhesion molecules, producing cytokines, and supporting leukocyte transmigration.
• Dynamic barrier properties were maintained and responsive to vascular permeability factors.
• Biomechanical and pharmacological stimuli induced relevant atheroprotective and atheroprone phenotypes.

Conclusions:

• Human iPSC-derived endothelium provides a valuable cellular platform with significant functional plasticity.
• This platform is suitable for cell-based assays investigating endothelial roles in inflammatory and cardiovascular diseases.
• iPSC technology overcomes limitations of patient-specific endothelial cell availability for disease modeling.