Artificial mesenchymal stem cell extracellular vesicles enhanced ischemic stroke treatment through targeted remodeling brain microvascular endothelial cells.
10.1016/j.apsb.2025.06.009
- Author:
Shengnan LI
1
;
Wei LV
2
;
Jiangna XU
1
;
Jiaqing YIN
1
;
Yuqin CHEN
1
;
Linfeng LIU
1
;
Xiang CAO
1
;
Wenjing LI
3
;
Zhen LI
3
;
Hua CHEN
4
;
Hongliang XIN
1
Author Information
1. Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
2. Department of Pharmacy, the Affiliated Jiangyin Hospital of Xuzhou Medical University, Wuxi 214400, China.
3. College of Pharmacy, Dalian Medical University, Dalian 116044, China.
4. Department of Neurosurgery, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Artificial extracellular vesicles;
Blood‒brain barrier;
Cerebral vascular endothelial cells;
Ischemic stroke therapy;
Mesenchymal stem cell membrane proteins;
Oxidative stress;
miR-132-3p
- From:
Acta Pharmaceutica Sinica B
2025;15(8):4248-4264
- CountryChina
- Language:English
-
Abstract:
Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the HII phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).
