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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Exosomal microRNAs from mesenchymal stem/stromal cells: Biology and applications in neuroprotection
Aida Nasirishargh, Priyadarsini Kumar, Lalithasri Ramasubramanian, Kaitlin Clark, Dake Hao, Sabrina V Lazar, Aijun Wang
Aida Nasirishargh, Priyadarsini Kumar, Lalithasri Ramasubramanian, Kaitlin Clark, Dake Hao, Sabrina V Lazar, Aijun Wang, Surgical Bioengineering Laboratory, Department of Surgery, University of California, Davis School of Medicine, Sacramento, CA 95817, United States
Priyadarsini Kumar, Kaitlin Clark, Dake Hao, Aijun Wang, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, United States
Lalithasri Ramasubramanian, Aijun Wang, Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, United States
Author contributions: Wang A and Nasirishargh A contributed to conceptualization; Nasirishargh A contributed to writing-original draft preparation; Nasirishargh A, Kumar P, Ramasubramanian L, Clark K, Hao D, Lazar SV and Wang A contributed to writing-drafting, editing and revising; Nasirishargh A contributed to visualization.
Supported by the National Institute on Aging of the National Institutes of Health under Award No. P30AG010129 through the UC Davis Alzheimer's Disease Center Pilot Program, No. 5R01NS100761-02 and No. 1R01NS115860-01A1; the Shriners Hospitals for Children Research Grants, No. 85108-NCA-19 and No. 85135-NCA-21; and the Shriners Hospitals for Children Postdoctoral Fellowship, No. 84705-NCA-19. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Aijun Wang, PhD, Professor, Co-Director, Surgical Bioengineering Laboratory, Department of Surgery, University of California, Davis School of Medicine, 4625 2nd Ave., Suit 3005, Sacramento, CA 95817, United States. aawang@ucdavis.edu
Received: February 9, 2021
Peer-review started: February 9, 2021
First decision: March 30, 2021
Revised: April 29, 2021
Accepted: June 22, 2021
Article in press: June 22, 2021
Published online: July 26, 2021
Mesenchymal stem/stromal cells (MSCs) are extensively studied as cell-therapy agents for neurological diseases. Recent studies consider exosomes secreted by MSCs as important mediators for MSCs’ neuroprotective functions. Exosomes transfer functional molecules including proteins, lipids, metabolites, DNAs, and coding and non-coding RNAs from MSCs to their target cells. Emerging evidence shows that exosomal microRNAs (miRNAs) play a key role in the neuroprotective properties of these exosomes by targeting several genes and regulating various biological processes. Multiple exosomal miRNAs have been identified to have neuroprotective effects by promoting neurogenesis, neurite remodeling and survival, and neuroplasticity. Thus, exosomal miRNAs have significant therapeutic potential for neurological disorders such as stroke, traumatic brain injury, and neuroinflammatory or neurodegenerative diseases and disorders. This review discusses the neuroprotective effects of selected miRNAs (miR-21, miR-17-92, miR-133, miR-138, miR-124, miR-30, miR146a, and miR-29b) and explores their mechanisms of action and applications for the treatment of various neurological disease and disorders. It also provides an overview of state-of-the-art bioengineering approaches for isolating exosomes, optimizing their yield and manipulating the miRNA content of their cargo to improve their therapeutic potential.
Core Tip: Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells, which, due to their high availability and their reparative abilities, have been developed as therapeutic agents for various neurological diseases. MSC-derived exosomes have been receiving increased attention for their therapeutic capacity and low adverse effects. This review summarizes recent research on the neuroprotective effects of selected MSC-derived exosomal microRNAs (miRNAs) and provides an overview of their application potential in different neurological disorder disease models. It also discusses practical bioengineering approaches for isolating MSC-derived exosomes, manipulating their miRNA cargos, and improving their therapeutic abilities.
