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 E2/prostaglandin E2 receptor 4 (PGE2/EP4) signaling pathway in MSCs with EP4 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 EP4 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

Details

Title
EP 4 Antagonist‐Elicited Extracellular Vesicles from Mesenchymal Stem Cells Rescue Cognition/Learning Deficiencies by Restoring Brain Cellular Functions
Author
Shih‐Yin Chen 1 ; Meng‐Chieh Lin 1 ; Jia‐Shiuan Tsai 1 ; Pei‐Lin He 1 ; Wen‐Ting Luo 1 ; Herschman, Harvey 2 ; Hua‐Jung Li 1   VIAFID ORCID Logo 

 Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan, Republic of China 
 Department of Molecular & Medical Pharmacology, University of California, Los Angeles, Los Angeles, California, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, California, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA 
Pages
707-723
Section
Tissue Engineering and Regenerative Medicine
Publication year
2019
Publication date
Jul 2019
Publisher
Oxford University Press
ISSN
21576564
e-ISSN
21576580
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2248368671
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.