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Endothelial Cell-Based Vascular Bandages for Blood-Brain Barrier Repair and Targeted siRNA Delivery
Yaosheng Li1,2, Yunfei Dong1, Yaode He3
1State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 8, 2026
Summary
This study introduces brain microvascular endothelial cell (mEC)-based vascular bandages to repair the blood-brain barrier (BBB) after stroke. This novel therapy targets and supports BBB recovery, reducing brain injury.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Regenerative Medicine
Background:
- Cerebral ischemia/reperfusion injury involves critical blood-brain barrier (BBB) disruption.
- Early BBB targeting and support are crucial for mitigating reperfusion injury.
- Existing therapies lack effective BBB repair mechanisms.
Purpose of the Study:
- To develop a novel therapeutic strategy for cerebral ischemia/reperfusion injury.
- To create a brain-targeted delivery platform for BBB repair.
- To investigate the efficacy of mEC-based vascular bandages in restoring BBB function.
Main Methods:
- Utilized brain microvascular endothelial cells (mECs) as vascular bandages.
- mECs target damaged vessels via very late antigen-4 (VLA-4) interaction.
- Employed oxygen-glucose deprivation-treated mEC culture supernatants (OGD-SN) to modulate connexin 43 (CX43) expression.
- Delivered p66Shc siRNA to the damaged endothelium for BBB regulation.
Main Results:
- Vascular bandage treatment successfully targeted damaged cerebral blood vessels.
- mECs restored BBB permeability and structural integrity by forming new junction proteins.
- OGD-SN promoted CX43 expression, enhancing therapeutic siRNA delivery.
- Treatment rescued BBB function, alleviated reperfusion injury, and reduced infarct size.
Conclusions:
- mEC-based vascular bandages offer a promising therapeutic strategy for cerebral ischemia/reperfusion injury.
- This approach provides a novel brain-targeted delivery platform for BBB repair.
- The study demonstrates successful mitigation of reperfusion injury through BBB restoration.
