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      • Record: found
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      Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm

      review-article
      Author(s): 2 , 1 , , 1 ,
      Publication date (Electronic):
      Journal: Biomarker Research
      Publisher: BioMed Central
      Keywords: Exosomes, Mesenchymal stem cell, Clinical trial, Disease

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          Abstract

          Mesenchymal stem/stromal cells (MSCs) have been demonstrated to hold great potential for the treatment of several diseases. Their therapeutic effects are largely mediated by paracrine factors including exosomes, which are nanometer-sized membrane-bound vesicles with functions as mediators of cell-cell communication. MSC-derived exosomes contain cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. Increasing evidence suggests that MSC-derived exosomes might represent a novel cell-free therapy with compelling advantages over parent MSCs such as no risk of tumor formation and lower immunogenicity. This paper reviews the characteristics of MSC exosomes and their fate after in vivo administration, and highlights the therapeutic potential of MSC-derived exosomes in liver, kidney, cardiovascular and neurological disease. Particularly, we summarize the recent clinical trials performed to evaluate the safety and efficacy of MSC exosomes. Overall, this paper provides a general overview of MSC-exosomes as a new cell-free therapeutic paradigm.

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          ExoCarta: A Web-Based Compendium of Exosomal Cargo.

          Shivakumar Keerthikumar, David Chisanga, Dinuka Ariyaratne … (2016)
          Exosomes are membranous vesicles that are released by a variety of cells into the extracellular microenvironment and are implicated in intercellular communication. As exosomes contain RNA, proteins and lipids, there is a significant interest in characterizing the molecular cargo of exosomes. Here, we describe ExoCarta (http://www.exocarta.org), a manually curated Web-based compendium of exosomal proteins, RNAs and lipids. Since its inception, the database has been highly accessed (>54,000 visitors from 135 countries). The current version of ExoCarta hosts 41,860 proteins, >7540 RNA and 1116 lipid molecules from more than 286 exosomal studies annotated with International Society for Extracellular Vesicles minimal experimental requirements for definition of extracellular vesicles. Besides, ExoCarta features dynamic protein-protein interaction networks and biological pathways of exosomal proteins. Users can download most often identified exosomal proteins based on the number of studies. The downloaded files can further be imported directly into FunRich (http://www.funrich.org) tool for additional functional enrichment and interaction network analysis.
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            Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter.

            Charles P. Lai, Osama Mardini, Maria Ericsson … (2014)
            Extracellular vesicles (EVs) are nanosized vesicles released by normal and diseased cells as a novel form of intercellular communication and can serve as an effective therapeutic vehicle for genes and drugs. Yet, much remains unknown about the in vivo properties of EVs such as tissue distribution, blood levels, and urine clearance, important parameters that will define their therapeutic effectiveness and potential toxicity. Here we combined Gaussia luciferase and metabolic biotinylation to create a sensitive EV reporter (EV-GlucB) for multimodal imaging in vivo, as well as monitoring of EV levels in the organs and biofluids ex vivo after administration of EVs. Bioluminescence and fluorescence-mediated tomography imaging on mice displayed a predominant localization of intravenously administered EVs in the spleen followed by the liver. Monitoring EV signal in the organs, blood, and urine further revealed that the EVs first undergo a rapid distribution phase followed by a longer elimination phase via hepatic and renal routes within six hours, which are both faster than previously reported using dye-labeled EVs. Moreover, we demonstrate systemically injected EVs can be delivered to tumor sites within an hour following injection. Altogether, we show the EVs are dynamically processed in vivo with accurate spatiotemporal resolution and target a number of normal organs as well as tumors with implications for disease pathology and therapeutic design.
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              Microvesicles Derived from Mesenchymal Stem Cells Enhance Survival in a Lethal Model of Acute Kidney Injury

              Stefania Bruno, Cristina Grange, Federica Collino … (2012)
              Several studies demonstrated that treatment with mesenchymal stem cells (MSCs) reduces cisplatin mortality in mice. Microvesicles (MVs) released from MSCs were previously shown to favor renal repair in non lethal toxic and ischemic acute renal injury (AKI). In the present study we investigated the effects of MSC-derived MVs in SCID mice survival in lethal cisplatin-induced AKI. Moreover, we evaluated in vitro the effect of MVs on cisplatin-induced apoptosis of human renal tubular epithelial cells and the molecular mechanisms involved. Two different regimens of MV injection were used. The single administration of MVs ameliorated renal function and morphology, and improved survival but did not prevent chronic tubular injury and persistent increase in BUN and creatinine. Multiple injections of MVs further decreased mortality and at day 21 surviving mice showed normal histology and renal function. The mechanism of protection was mainly ascribed to an anti-apoptotic effect of MVs. In vitro studies demonstrated that MVs up-regulated in cisplatin-treated human tubular epithelial cells anti-apoptotic genes, such as Bcl-xL, Bcl2 and BIRC8 and down-regulated genes that have a central role in the execution-phase of cell apoptosis such as Casp1, Casp8 and LTA. In conclusion, MVs released from MSCs were found to exert a pro-survival effect on renal cells in vitro and in vivo, suggesting that MVs may contribute to renal protection conferred by MSCs.
              Article 0 comments Cited 252 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Shihua Wang: wangshihua@ibms.pumc.edu.cn
                Robert Chunhua Zhao: zhaochunhua@ibms.pumc.edu.cn
                Journal
                Journal ID (nlm-ta): Biomark Res
                Journal ID (iso-abbrev): Biomark Res
                Title: Biomarker Research
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2050-7771
                Publication date (Electronic): 4 April 2019
                Publication date PMC-release: 4 April 2019
                Publication date Collection: 2019
                Volume: 7
                Electronic Location Identifier: 8
                Affiliations
                [1 ]ISNI 0000 0001 0662 3178, GRID grid.12527.33, Center of Excellence in Tissue Engineering, Department of cell biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, , School of Basic Medicine Peking Union Medical College, ; Beijing, China
                [2 ]ISNI 0000 0001 0455 0905, GRID grid.410645.2, Department of Biochemistry and Molecular biology, Basic medical college, , Qingdao University, ; 308 Ningxia Road, Qingdao, 266071 China
                Article
                Publisher ID: 159
                DOI: 10.1186/s40364-019-0159-x
                PMC ID: 6450000
                PubMed ID: 30992990
                SO-VID: 1a556d26-69c6-472f-9843-99220f4e3c46
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 29 January 2019
                Date accepted : 27 March 2019
                Funding
                Funded by: CAMS Innovation Fund for Medical Sciences
                Award ID: 2017-I2M-3-007
                Award Recipient :
                Funded by: State Key Laboratory of Power Transmission Equipment and System Security (CN)
                Award ID: BZ0381
                Award Recipient :
                Funded by: Qingdao University newly introduced talent research start-up fee
                Award ID: 41117010251
                Award Recipient :
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                Keywords: exosomes,mesenchymal stem cell,clinical trial,disease
                Data availability:
                Keywords: exosomes, mesenchymal stem cell, clinical trial, disease

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