The first abdominal aortic aneurysm organoid model replicates complex microenvironment for in vitro disease study

Area of Science:

• Vascular Biology
• Regenerative Medicine
• Organoid Technology

Background:

• Abdominal Aortic Aneurysm (AAA) affects up to 8% of men over 65, with complex causes like smoking and age.
• Current treatment options for AAA are limited, highlighting the need for advanced in vitro models.
• Developing a reliable model is crucial for understanding AAA pathophysiology and for ex vivo drug screening.

Purpose of the Study:

• To develop and validate a novel patient-derived organoid (PDO) model for Abdominal Aortic Aneurysm (AAA).
• To establish a 3D in vitro system that mimics the AAA microenvironment for disease modeling.
• To assess the model's stability, pathological relevance, and utility for pharmacological testing.

Main Methods:

• Utilized a non-enzymatic, Matrigel-free procedure with specialized medium for AAA PDO generation.
• Assessed model stability via microscopy, H&E staining, immunohistochemistry (IHC), viability assays, and whole-genome sequencing (WES).
• Conducted preliminary pharmacological assessments using mass spectrometry to evaluate drug responses.

Main Results:

• The AAA PDO model preserved aortic morphology, pathological features, and the immune microenvironment (macrophages, lymphocytes).
• Model stability was confirmed by consistent genetic mutations (WES) and cell viability for five weeks.
• Preliminary drug screening showed distinct responses to metformin, RU.521, and STING-IN-2.

Conclusions:

• This represents the first reported patient-derived organoid model for abdominal aortic aneurysm (AAA).
• The AAA PDO model serves as a valuable tool for studying AAA pathophysiology.
• This model shows promise for ex vivo drug testing and could complement current surgical treatments for AAA.