In Vitro Modeling of Atherosclerosis Using iPSC-Derived Blood Vessel Organoids

Area of Science:

• Vascular Biology
• Stem Cell Biology
• Biomedical Engineering

Background:

• In vitro models for atherosclerosis lack complex 3D vascular structures.
• Induced pluripotent stem cell-derived blood vessel organoids (BVOs) offer a promising 3D vascular model.
• BVOs self-assemble with multiple cell types, mimicking native vasculature.

Purpose of the Study:

• To develop and validate an advanced in vitro model for atherosclerosis.
• To investigate the therapeutic efficacy of nano-sized graphene oxides (NGOs) in an atherosclerosis model.
• To establish a platform for drug discovery and personalized medicine in vascular diseases.

Main Methods:

• Generation of atherosclerotic blood vessel organoids (BVOs) with atherogenic microenvironment factors.
• Co-culture of BVOs with monocytes to induce inflammatory responses.
• Treatment of atherosclerotic BVOs with lovastatin and nano-sized graphene oxides (NGOs).
• Assessment of atherosclerotic phenotypes and drug efficacy through various assays.

Main Results:

• Atherosclerotic BVOs recapitulated key phenotypes: endothelial dysfunction, foam cell formation, fibrous plaque, and calcification.
• Lovastatin treatment attenuated atherosclerotic phenotypes in the BVO model.
• Nano-sized graphene oxides (NGOs) reduced pathologic lesions by promoting M2 macrophage polarization.
• The model demonstrated responsiveness to known therapeutic interventions.

Conclusions:

• Atherosclerotic BVOs represent an advanced in vitro model for studying vascular diseases.
• This platform is suitable for drug discovery, mechanism elucidation, and personalized drug screening.
• Patient-derived BVOs hold potential for precision medicine applications in atherosclerosis.