Stem cell-derived vessels-on-chip for cardiovascular disease modeling.

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Stem Cell Technology

Background:

• Metabolic syndrome leads to vascular complications, necessitating better in vitro models.
• Current models lack the complexity to fully replicate human vascular dysfunction.
• Human pluripotent stem cell-derived endothelial cells (SC-ECs) offer a promising cell source for disease modeling.

Purpose of the Study:

• To engineer an advanced open microfluidic vessel-on-chip platform.
• To mature SC-ECs and model early-onset atherosclerosis.
• To enable patient-specific vascular tissue modeling and animal-free research.

Main Methods:

• Development of an open microfluidic platform integrating SC-ECs.
• Utilizing gravity-driven flow to promote SC-EC maturation (barrier formation, arterial toning, nitric oxide synthesis).
• Employing single-cell RNA sequencing, proteomics, and high-resolution imaging for analysis.
• Stimulating SC-ECs with oxidized low-density lipoprotein and free fatty acids to induce disease hallmarks.

Main Results:

• Achieved significant SC-EC maturation, including barrier function and high nitric oxide production.
• Successfully modeled early-onset atherosclerosis hallmarks using low cell numbers and volumes.
• Identified key proteome and secretome changes in response to atherogenic stimuli.
• Demonstrated the platform's capability for advanced analytical technology integration.

Conclusions:

• The engineered vessel-on-chip platform provides a robust model for studying vascular complications of metabolic syndrome.
• This technology enables detailed analysis of endothelial cell function and disease mechanisms.
• The platform supports patient-specific modeling and advances animal-free vascular research.