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      Novel insights into MSC-EVs therapy for immune diseases

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          Abstract

          Mesenchymal stromal cells (MSC) are a heterogeneous cell population with self-renewal and the ability to differentiate into different lineages. The novel regulatory role of MSC in both adaptive and innate immune responses got extensive investigation and MSC have been widely used in clinical trials as immunosuppressive agents for autoimmune and inflammatory diseases, including graft-versus-host disease (GVHD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), chronic kidney disease, etc. Recent studies have found that MSC exerted their immunomodulation function through secreting extracellular vesicles (EVs), which delivered parent cell cargo to recipient cells without oncogenicity or variability. Since MSC-EVs exhibit most of the properties of MSC and take advantage of their cellular immunomodulatory fuction, MSC-EVs appear to a promising none-cell therapy in various human diseases. In this review, we summarize the pivotal roles of MSC-EVs as agents for immunotherapy in diseases.

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          Most cited references59

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          Origins and Mechanisms of miRNAs and siRNAs.

          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
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            Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.

            Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now well after 1 year. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.
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              Using exosomes, naturally-equipped nanocarriers, for drug delivery.

              Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations.
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                Author and article information

                Contributors
                lai_peilong@163.com
                wengjianyu1969@163.com
                1509811071@qq.com
                874343960@qq.com
                miyadu@hotmail.com
                Journal
                Biomark Res
                Biomark Res
                Biomarker Research
                BioMed Central (London )
                2050-7771
                18 March 2019
                18 March 2019
                2019
                : 7
                : 6
                Affiliations
                [1 ]GRID grid.410643.4, Department of Hematology, Guangdong Provincial People’s Hospital, , Guangdong Academy of Medical Sciences, ; Guangzhou, Guangdong 510080 People’s Republic of China
                [2 ]ISNI 0000 0004 1760 3705, GRID grid.413352.2, Guangdong Geriatrics Institute, ; Guangzhou, Guangdong 510080 People’s Republic of China
                Article
                156
                10.1186/s40364-019-0156-0
                6423844
                30923617
                161ea366-4dfb-4add-b930-a8e5d1c41dd7
                © The Author(s). 2019

                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
                : 1 December 2018
                : 27 February 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81671585
                Award ID: 81870121
                Award Recipient :
                Funded by: Science and Technology Planning Project of Guangzhou, China
                Award ID: 201803040011 and 201803040005
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                mesenchymal stromal cells,extracellular vesicles,immunomodulation,graft-versus-host disease,inflammatory diseases

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