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A High Output Method to Isolate Cerebral Pericytes from Mouse
Published on: January 14, 2020
Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and
Weiwei Shen1, Weishi Liu1, Min Guo1
1Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China.
Journal of Extracellular Vesicles
|June 2, 2026
Summary
Engineered extracellular vesicles (EVs) targeting brain pericytes show promise for treating vascular cognitive impairment (VCI). These cNGR-EVs protect against brain hypoperfusion and cognitive decline by stabilizing the neurovascular unit.
Area of Science:
- Neuroscience
- Biotechnology
- Vascular Biology
Background:
- Pericyte dysfunction is a key early indicator of vascular cognitive impairment (VCI).
- Current therapies for VCI targeting pericytes are limited.
- Developing targeted strategies to address pericyte dysfunction is crucial for VCI treatment.
Purpose of the Study:
- To engineer extracellular vesicles (EVs) for targeted delivery to brain pericytes.
- To evaluate the therapeutic potential of cyclic NGR (cNGR)-functionalized EVs (cNGR-EVs) in a mouse model of chronic cerebral hypoperfusion (BCAS).
- To investigate the effects of cNGR-EVs on pericyte function, neurovascular unit integrity, and cognitive performance.
Main Methods:
- Bio-orthogonal engineering of EVs with cNGR peptides for pericyte targeting.
- In vitro and in vivo validation of cNGR-EVs targeting CD13-expressing brain pericytes.
- Assessment of cNGR-EVs in a mouse model of chronic cerebral hypoperfusion (BCAS).
- Analysis of pericyte function, blood-brain barrier integrity, myelination, cognitive performance, and gene expression profiles using single-cell RNA sequencing.
Main Results:
- cNGR-EVs demonstrated efficient targeting of brain pericytes both in vitro and in vivo.
- In the BCAS mouse model, cNGR-EVs preserved pericyte contractility and protected against cerebral hypoperfusion.
- Treatment with cNGR-EVs reduced blood-brain barrier leakage, attenuated demyelination, and improved cognitive function.
- Single-cell RNA sequencing revealed that cNGR-EVs normalized BCAS-induced transcriptional changes in pericytes and downstream neuronal and glial cells.
Conclusions:
- cNGR-EVs represent a promising pericyte-targeted therapeutic strategy for early VCI.
- This approach stabilizes the neurovascular unit and maintains pericyte function.
- cNGR-EVs effectively prevent cognitive decline and myelin loss in a VCI model, highlighting pericytes as a viable therapeutic target.
