Intravenously injected hPSC-derived pericytes for Alzheimer disease: Neuroprotection and vascular repair via extracellular vesicles

TL;DR

Injecting pericytes from stem cells helps treat Alzheimer's by improving memory and reducing brain damage through their tiny vesicles.

Contribution

The study shows that extracellular vesicles from hPSC-derived pericytes can treat Alzheimer's by reducing amyloid and repairing the brain's blood vessels.

Findings

Intravenous hPSC-CNC PCs improved memory and reduced β-amyloid in AD mice.

EVs from hPSC-CNC PCs repaired the blood-brain barrier and enhanced neurovascular function.

miRNA-486-5p in EVs may promote neurovascular repair through multiple mechanisms.

Abstract

Intravenously injected human pluripotent stem cell (hPSC)-derived pericytes (PCs) and their extracellular vesicles (EVs) represent promising therapeutic strategies for neurological diseases. Our study aimed to investigate the effects and mechanisms of intravenous transplantation for treating Alzheimer disease (AD), with a focus on elucidating the critical role of EV-related mechanisms. We generated PCs (hPSC-CNC PCs) from hPSC-derived cranial neural crest (CNC) and employed 12-month-old 5xFAD mice as an advanced stage AD model. We investigated memory function, intracerebral β-amyloid (Aβ) deposition, blood-brain barrier (BBB) permeability, neuronal morphology, and associated protein expressions in mice to determine the therapeutic effects of intravenous administration of hPSC-CNC PCs or EVs. miRNA sequencing was conducted to identify potential downstream pathways. We found that intravenous administration of hPSC-CNC PCs improved memory function of aged AD mice, concurrently reducing pathological deposits and BBB leakage and enhancing neurofunctional outcomes via EVs. Furthermore, miRNA-486-5p in EVs might promote neurovascular repair through various mechanisms. Our results demonstrated that EVs from hPSC-CNC PCs exert protective effects against AD.

Yamei Tang and colleagues investigated the therapeutic potential of human pluripotent stem cell-derived pericytes and their extracellular vesicles (EVs) for Alzheimer disease (AD). Their findings reveal that intravenous administration of these EVs improves memory, reduces β-amyloid deposition, and enhances neurovascular repair, offering a promising strategy for AD treatment.

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