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      Exosomes and Stem Cells in Degenerative Disease Diagnosis and Therapy

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          Abstract

          Stroke can cause death and disability, resulting in a huge burden on society. Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by motor dysfunction. Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage destruction and osteophyte formation in the joints. Stem cell therapy may provide a biological treatment alternative to traditional pharmacological therapy. Mesenchymal stem cells (MSCs) are preferred because of their differentiation ability and possible derivation from many adult tissues. In addition, the paracrine effects of MSCs play crucial anti-inflammatory and immunosuppressive roles in immune cells. Extracellular vesicles (EVs) are vital mediators of cell-to-cell communication. Exosomes contain various molecules such as microRNA (miRNA), which mediates biological functions through gene regulation. Therefore, exosomes carrying miRNA or other molecules can enhance the therapeutic effects of MSC transplantation. MSC-derived exosomes have been investigated in various animal models representing stroke, PD, and OA. Exosomes are a subtype of EVs. This review article focuses on the mechanism and therapeutic potential of MSC-derived exosomes in stroke, PD, and OA in basic and clinical aspects.

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          Physiological and pathological roles for microRNAs in the immune system.

          Ryan O'Connell, Dinesh Rao, Aadel Chaudhuri … (2010)
          Mammalian microRNAs (miRNAs) have recently been identified as important regulators of gene expression, and they function by repressing specific target genes at the post-transcriptional level. Now, studies of miRNAs are resolving some unsolved issues in immunology. Recent studies have shown that miRNAs have unique expression profiles in cells of the innate and adaptive immune systems and have pivotal roles in the regulation of both cell development and function. Furthermore, when miRNAs are aberrantly expressed they can contribute to pathological conditions involving the immune system, such as cancer and autoimmunity; they have also been shown to be useful as diagnostic and prognostic indicators of disease type and severity. This Review discusses recent advances in our understanding of both the intended functions of miRNAs in managing immune cell biology and their pathological roles when their expression is dysregulated.
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            Adult mesenchymal stem cells for tissue engineering versus regenerative medicine.

            Arnold I. Caplan (2007)
            Adult mesenchymal stem cells (MSCs) can be isolated from bone marrow or marrow aspirates and because they are culture-dish adherent, they can be expanded in culture while maintaining their multipotency. The MSCs have been used in preclinical models for tissue engineering of bone, cartilage, muscle, marrow stroma, tendon, fat, and other connective tissues. These tissue-engineered materials show considerable promise for use in rebuilding damaged or diseased mesenchymal tissues. Unanticipated is the realization that the MSCs secrete a large spectrum of bioactive molecules. These molecules are immunosuppressive, especially for T-cells and, thus, allogeneic MSCs can be considered for therapeutic use. In this context, the secreted bioactive molecules provide a regenerative microenvironment for a variety of injured adult tissues to limit the area of damage and to mount a self-regulated regenerative response. This regenerative microenvironment is referred to as trophic activity and, therefore, MSCs appear to be valuable mediators for tissue repair and regeneration. The natural titers of MSCs that are drawn to sites of tissue injury can be augmented by allogeneic MSCs delivered via the bloodstream. Indeed, human clinical trials are now under way to use allogeneic MSCs for treatment of myocardial infarcts, graft-versus-host disease, Crohn's Disease, cartilage and meniscus repair, stroke, and spinal cord injury. This review summarizes the biological basis for the in vivo functioning of MSCs through development and aging.
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              Exosome secretion: molecular mechanisms and roles in immune responses.

              Angélique Bobrie, Marina Colombo, Graça Raposo … (2011)
              Exosomes are small membrane vesicles, secreted by most cell types from multivesicular endosomes, and thought to play important roles in intercellular communications. Initially described in 1983, as specifically secreted by reticulocytes, exosomes became of interest for immunologists in 1996, when they were proposed to play a role in antigen presentation. More recently, the finding that exosomes carry genetic materials, mRNA and miRNA, has been a major breakthrough in the field, unveiling their capacity to vehicle genetic messages. It is now clear that not only immune cells but probably all cell types are able to secrete exosomes: their range of possible functions expands well beyond immunology to neurobiology, stem cell and tumor biology, and their use in clinical applications as biomarkers or as therapeutic tools is an extensive area of research. Despite intensive efforts to understand their functions, two issues remain to be solved in the future: (i) what are the physiological function(s) of exosomes in vivo and (ii) what are the relative contributions of exosomes and of other secreted membrane vesicles in these proposed functions? Here, we will focus on the current ideas on exosomes and immune responses, but also on their mechanisms of secretion and the use of this knowledge to elucidate the latter issue. © 2011 John Wiley & Sons A/S.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cell Transplant
                Journal ID (iso-abbrev): Cell Transplant
                Journal ID (publisher-id): CLL
                Journal ID (hwp): spcll
                Title: Cell Transplantation
                Publisher: SAGE Publications (Sage CA: Los Angeles, CA )
                ISSN (Print): 0963-6897
                ISSN (Electronic): 1555-3892
                Publication date (Electronic): 25 April 2018
                Publication date (Print): March 2018
                Volume: 27
                Issue: 3
                Pages: 349-363
                Affiliations
                [1 ]Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
                [2 ]Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
                [3 ]Department of Orthopedics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
                [4 ]Department of Pathology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
                [5 ]Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
                [6 ]Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
                Author notes
                [*]Dah-Ching Ding, Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, No. 707, Chung-Yang Road, Section 3, Hualien, Taiwan. Email: dah1003@ 123456yahoo.com.tw
                Article
                Publisher ID: 10.1177_0963689717723636
                DOI: 10.1177/0963689717723636
                PMC ID: 6038041
                PubMed ID: 29692195
                SO-VID: cb88b525-18bb-4ad4-8ea3-e1954b894792
                Copyright © © The Author(s) 2018
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 14 December 2016
                Date revision received : 06 June 2017
                Date accepted : 03 July 2017
                Categories
                Subject: Reviews

                Keywords: stroke,parkinson’s disease,osteoarthritis,mesenchymal stem cells,exosomes,mirna
                Data availability:
                Keywords: stroke, parkinson’s disease, osteoarthritis, mesenchymal stem cells, exosomes, mirna

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