Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Vascular Biology

Background:

• Extracellular vesicles (EVs) from bone marrow mesenchymal stem cells (BM-MSCs) show therapeutic promise for abdominal aortic aneurysms (AAAs).
• Systemic delivery of EVs results in poor homing to injury sites, limiting their therapeutic efficacy.
• Targeted delivery strategies are crucial for effective EV-based therapies.

Purpose of the Study:

• To develop a surface modification strategy for targeting BM-MSC-derived EVs to the abdominal aortic aneurysm (AAA) wall.
• To enhance the affinity of EVs for AAA-specific targets, improving their therapeutic delivery.

Main Methods:

• Postisolation surface modification of EVs using copper-free click chemistry.
• Conjugation of EVs with an azide-modified peptide targeting cathepsin K (CatK), which is overexpressed in AAA walls.
• Assessment of EV uptake in cultured aneurysmal smooth muscle cells (SMCs) and binding to ex vivo vessel walls.

Main Results:

• Peptide conjugation significantly improved EV uptake into cultured aneurysmal SMCs.
• Modified EVs demonstrated enhanced binding to the walls of matrix-injured vessels ex vivo.
• The proregenerative and antiproteolytic effects of MSC-EVs were preserved after peptide conjugation.

Conclusions:

• Surface modification of EVs with short synthetic peptides is an effective strategy for enhancing cell-specific uptake.
• This approach holds promise for facilitating targeted therapy in abdominal aortic aneurysms (AAAs).
• Targeted EVs could improve treatment outcomes for aortic wall pathologies.