Open AccessEP 4 Antagonist‐Elicited Extracellular Vesicles from Mesenchymal Stem Cells Rescue Cognition/Learning Deficiencies by Restoring Brain Cellular Functions
Author(s) -
Chen ShihYin,
Lin MengChieh,
Tsai JiaShiuan,
He PeiLin,
Luo WenTing,
Herschman Harvey,
Li HuaJung
Publication year - 2019
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.18-0284
Subject(s) - mesenchymal stem cell , astrogliosis , stem cell , astrocyte , extracellular vesicle , microglia , microbiology and biotechnology , neurogenesis , blood–brain barrier , inflammation , hippocampal formation , biology , medicine , neuroscience , pharmacology , immunology , microvesicles , central nervous system , microrna , biochemistry , gene
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 2 /prostaglandin E 2 receptor 4 (PGE 2 /EP 4 ) signaling pathway in MSCs with EP 4 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 4 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