Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke

Abolfazl Rahmani; Kiarash Saleki; Nima Javanmehr; Javad Khodaparast; Payam Saadat; Hamid Reza Nouri

doi:10.1016/j.arr.2020.101106

Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke

Ageing Res Rev. 2020 Sep:62:101106. doi: 10.1016/j.arr.2020.101106. Epub 2020 Jun 18.

Authors

Abolfazl Rahmani¹, Kiarash Saleki¹, Nima Javanmehr¹, Javad Khodaparast¹, Payam Saadat², Hamid Reza Nouri³

Affiliations

¹ Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
² Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
³ Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Electronic address: h.noori@mubabol.ac.ir.

PMID: 32565329
DOI: 10.1016/j.arr.2020.101106

Abstract

Stem cell-based treatments have been suggested as promising candidates for stroke. Recently, mesenchymal stem cells (MSCs) have been reported as potential therapeutics for a wide range of diseases. In particular, clinical trial studies have suggested MSCs for stroke therapy. The focus of MSC treatments has been directed towards cell replacement. However, recent research has lately highlighted their paracrine actions. The secretion of extracellular vesicles (EVs) is offered to be the main therapeutic mechanism of MSC therapy. However, EV-based treatments may provide a wider therapeutic window compared to tissue plasminogen activator (tPA), the traditional treatment for stroke. Exosomes are nano-sized EVs secreted by most cell types, and can be isolated from conditioned cell media or body fluids such as plasma, urine, and cerebrospinal fluid (CSF). Exosomes apply their effects through targeting their cargos such as microRNAs (miRs), DNAs, messenger RNAs, and proteins at the host cells, which leads to a shift in the behavior of the recipient cells. It has been indicated that exosomes, in particular their functional cargoes, play a significant role in the coupled pathogenesis and recovery of stroke through affecting the neurovascular unit (NVU). Therefore, it seems that exosomes could be utilized as diagnostic and therapeutic tools in stroke treatment. The miRs are small endogenous non-coding RNA molecules which serve as the main functional cargo of exosomes, and apply their effects as epigenetic regulators. These versatile non-coding RNA molecules are involved in various stages of stroke and affect stroke-related factors. Moreover, the involvement of aging-induced changes to specific miRs profile in stroke further highlights the role of miRs. Thus, miRs could be utilized as diagnostic, prognostic, and therapeutic tools in stroke. In this review, we discuss the roles of stem cells, exosomes, and their application in stroke therapy. We also highlight the usage of miRs as a therapeutic choice in stroke therapy.

Keywords: Exosomes; MicroRNAs; Stem cell-based treatments; Stroke.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Exosomes*
Extracellular Vesicles*
Humans
Mesenchymal Stem Cells*
MicroRNAs / genetics
Stroke* / therapy
Tissue Plasminogen Activator

Substances

MicroRNAs
Tissue Plasminogen Activator