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      Mesenchymal stem cells’ “garbage bags” at work: Treating radial nerve injury with mesenchymal stem cell-derived exosomes

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          Abstract

          Unlike central nervous system injuries, peripheral nerve injuries (PNIs) are often characterized by more or less successful axonal regeneration. However, structural and functional recovery is a senile process involving multifaceted cellular and molecular processes. The contemporary treatment options are limited, with surgical intervention as the gold-standard method; however, each treatment option has its associated limitations, especially when the injury is severe with a large gap. Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI. The recent pilot study is a leap forward in the field, which is expected to pave the way for more enormous, systematic, and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach, in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

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          Most cited references75

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          Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth.

          Multipotent mesenchymal stromal cells (MSCs) have potential therapeutic benefit for the treatment of neurological diseases and injury. MSCs interact with and alter brain parenchymal cells by direct cell-cell communication and/or by indirect secretion of factors and thereby promote functional recovery. In this study, we found that MSC treatment of rats subjected to middle cerebral artery occlusion (MCAo) significantly increased microRNA 133b (miR-133b) level in the ipsilateral hemisphere. In vitro, miR-133b levels in MSCs and in their exosomes increased after MSCs were exposed to ipsilateral ischemic tissue extracts from rats subjected to MCAo. miR-133b levels were also increased in primary cultured neurons and astrocytes treated with the exosome-enriched fractions released from these MSCs. Knockdown of miR-133b in MSCs confirmed that the increased miR-133b level in astrocytes is attributed to their transfer from MSCs. Further verification of this exosome-mediated intercellular communication was performed using a cel-miR-67 luciferase reporter system and an MSC-astrocyte coculture model. Cel-miR-67 in MSCs was transferred to astrocytes via exosomes between 50 and 100 nm in diameter. Our data suggest that the cel-miR-67 released from MSCs was primarily contained in exosomes. A gap junction intercellular communication inhibitor arrested the exosomal microRNA communication by inhibiting exosome release. Cultured neurons treated with exosome-enriched fractions from MSCs exposed to 72 hours post-MCAo brain extracts significantly increased the neurite branch number and total neurite length. This study provides the first demonstration that MSCs communicate with brain parenchymal cells and may regulate neurite outgrowth by transfer of miR-133b to neural cells via exosomes. Copyright © 2012 AlphaMed Press.
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            Vesiclepedia 2019: a compendium of RNA, proteins, lipids and metabolites in extracellular vesicles

            Abstract Extracellular vesicles (EVs) are membranous vesicles that are released by both prokaryotic and eukaryotic cells into the extracellular microenvironment. EVs can be categorised as exosomes, ectosomes or shedding microvesicles and apoptotic bodies based on the mode of biogenesis. EVs contain biologically active cargo of nucleic acids, proteins, lipids and metabolites that can be altered based on the precise state of the cell. Vesiclepedia (http://www.microvesicles.org) is a web-based compendium of RNA, proteins, lipids and metabolites that are identified in EVs from both published and unpublished studies. Currently, Vesiclepedia contains data obtained from 1254 EV studies, 38 146 RNA entries, 349 988 protein entries and 639 lipid/metabolite entries. Vesiclepedia is publicly available and allows users to query and download EV cargo based on different search criteria. The mode of EV isolation and characterization, the biophysical and molecular properties and EV-METRIC are listed in the database aiding biomedical scientists in assessing the quality of the EV preparation and the corresponding data obtained. In addition, FunRich-based Vesiclepedia plugin is incorporated aiding users in data analysis.
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              Synaptic Plasticity Forms and Functions

              Synaptic plasticity, the activity-dependent change in neuronal connection strength, has long been considered an important component of learning and memory. Computational and engineering work corroborate the power of learning through the directed adjustment of connection weights. Here we review the fundamental elements of four broadly categorized forms of synaptic plasticity and discuss their functional capabilities and limitations. Although standard, correlation-based, Hebbian synaptic plasticity has been the primary focus of neuroscientists for decades, it is inherently limited. Three-factor plasticity rules supplement Hebbian forms with neuromodulation and eligibility traces, while true supervised types go even further by adding objectives and instructive signals. Finally, a recently discovered hippocampal form of synaptic plasticity combines the above elements, while leaving behind the primary Hebbian requirement. We suggest that the effort to determine the neural basis of adaptive behavior could benefit from renewed experimental and theoretical investigation of more powerful directed types of synaptic plasticity.
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                Author and article information

                Contributors
                Journal
                World J Stem Cells
                WJSC
                World Journal of Stem Cells
                Baishideng Publishing Group Inc
                1948-0210
                26 May 2024
                26 May 2024
                : 16
                : 5
                : 467-478
                Affiliations
                Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia
                Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia
                Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta 6632110, Egypt
                Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia
                Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia. kh.haider@ 123456sr.edu.sa
                Author notes

                Author contributions: Zineldeen DH contributed to writing and generating the visual abstract of this manuscript; Mushtaq M and Mateen MA were involved in writing up and revising this article; Mateen MA contributed to the figures; and Haider KH participated in writing, finalizing, and submitting the manuscript.

                Corresponding author: Khawaja Husnain Haider, BSc, BPharm, MPharm, PhD, Chairman, Full Professor, Department of Basic Sciences, Sulaiman AlRajhi University, AlMadina Road, Albukairiyah 52736, AlQaseem, Saudi Arabia. kh.haider@ 123456sr.edu.sa

                Article
                jWJSC.v16.i5.pg467 93132
                10.4252/wjsc.v16.i5.467
                11135253
                38817330
                1a989278-48cf-4517-bc95-2b9b3fa197b3
                ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.

                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.

                History
                : 20 February 2024
                : 3 April 2024
                : 25 April 2024
                Categories
                Editorial

                exosome,mesenchymal stem cells,nerve injury,stem cells,secretome,regeneration

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