EP Antagonist-Elicited Extracellular Vesicles from Mesenchymal Stem Cells Rescue Cognition/Learning Deficiencies by Restoring Brain Cellular Functions

Overview

Journal Stem Cells Transl Med

Publisher Oxford University Press

Specialties Cell Biology
Pharmacology

Date 2019 Mar 21

PMID 30891948

Citations 27

Authors

Shih-Yin Chen

Meng-Chieh Lin

Jia-Shiuan Tsai

Pei-Lin He

Wen-Ting Luo

Harvey Herschman

Hua-Jung Li

Affiliations

Soon will be listed here.

Abstract

Adult brains have limited regenerative capacity. Consequently, both brain damage and neurodegenerative diseases often cause functional impairment for patients. Mesenchymal stem cells (MSCs), one type of adult stem cells, can be isolated from various adult tissues. MSCs have been used in clinical trials to treat human diseases and the therapeutic potentials of the MSC-derived secretome and extracellular vesicles (EVs) have been under investigation. We found that blocking the prostaglandin E /prostaglandin E receptor 4 (PGE /EP ) signaling pathway in MSCs with EP antagonists increased EV release and promoted the sorting of specific proteins, including anti-inflammatory cytokines and factors that modify astrocyte function, blood-brain barrier integrity, and microglial migration into the damaged hippocampus, into the EVs. Systemic administration of EP antagonist-elicited MSC EVs repaired deficiencies of cognition, learning and memory, inhibited reactive astrogliosis, attenuated extensive inflammation, reduced microglial infiltration into the damaged hippocampus, and increased blood-brain barrier integrity when administered to mice following hippocampal damage. Stem Cells Translational Medicine 2019.

Citing Articles

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Composition, functions, and applications of exosomal membrane proteins.

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Exosomes: potential targets for the diagnosis and treatment of neuropsychiatric disorders.

Li H, Yuan Y, Xie Q, Dong Z J Transl Med. 2024; 22(1):115.

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The functions of exosomes targeting astrocytes and astrocyte-derived exosomes targeting other cell types.

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