Engineered Mesenchymal Stem Cell-Derived Extracellular Vesicles Reverse Endothelial-Mesenchymal Transition in...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Cardiovascular Research

Background:

• Endothelial-mesenchymal transition (EndMT) in vascular endothelial cells (VECs) is a key driver of atherosclerosis (AS) progression.
• Reversing EndMT presents a promising therapeutic strategy for AS treatment.

Purpose of the Study:

• To engineer bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) as targeted nanocarriers for AS therapy.
• To deliver silent information regulator 2-related enzyme 1 (SIRT1) to reverse EndMT in VECs.

Main Methods:

• Engineered EVs were functionalized with VECs-specific aptamers for targeting and overexpressed SIRT1 for therapeutic effect.
• The engineered EVs were designed to target and deliver SIRT1 to VECs, activating the Nrf2 pathway and regulating oxidative stress.
• In vitro and in vivo studies were conducted to evaluate the efficacy of the engineered EVs in reversing EndMT and reducing atherosclerotic plaque inflammation.

Main Results:

• Engineered EVs successfully targeted VECs and delivered SIRT1, leading to the reversal of EndMT.
• SIRT1 activation of Nrf2 and regulation of oxidative stress were confirmed.
• Significant reduction in inflammation within atherosclerotic plaques was observed in both in vitro and in vivo models.

Conclusions:

• Engineered EVs provide a novel and effective strategy for targeted AS therapy by reversing EndMT.
• This approach demonstrates the potential of regenerative medicine technologies using engineered EVs for cardiovascular diseases.