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      Noncoding RNAs from tissue-derived small extracellular vesicles: Roles in diabetes and diabetic complications

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          Abstract

          Diabetes is a systemic disease, and its progression involves multiple organ dysfunction. However, the exact mechanisms underlying pathological progression remain unclear. Small extracellular vesicles (sEVs) mediate physiological and pathological signaling communication between organs and have been shown to have important regulatory roles in diabetes and its complications in recent years. In particular, the majority of studies in the diabetes-related research field have focused on the noncoding RNAs carried by sEVs. Researchers found that noncoding RNA sorting into sEVs is not random but selective. Both tissue origin differences and environmental variations affect the cargo of sEVs. In addition, the function of sEVs differs according to the tissue they derive from; for example, sEVs derived from adipose tissue regulate insulin sensitivity in the periphery, while sEVs derived from bone marrow promote β-cell regeneration. Therefore, understanding the roles of sEVs from different tissues is important for elucidating their molecular mechanisms and is necessary for the application of sEVs as therapeutic agents for diabetes treatment in the future. In this review, we summarized current studies on the mechanisms of noncoding RNA sorting into sEVs, as well as the research progress on the effects of sEVs from different tissue origins and noncoding RNAs in diabetes and diabetic complications. The knowledge of noncoding RNAs in sEVs will help us better understand the role of sEVs in the diabetes progression.

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          Most cited references120

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

            The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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              Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

              Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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                Author and article information

                Contributors
                Journal
                Mol Metab
                Mol Metab
                Molecular Metabolism
                Elsevier
                2212-8778
                02 February 2022
                April 2022
                02 February 2022
                : 58
                : 101453
                Affiliations
                [1 ]Institute for Translational Medicine, The Affiliated Hospital, Qingdao University, Qingdao, China
                [2 ]School of Basic Medical Sciences, College of Medicine, Qingdao University, Qingdao, China
                [3 ]College of Medicine, Qingdao University, Qingdao, China
                Author notes
                []Corresponding author. Institute for Translational Medicine, The Affiliated Hospital, College of Medicine, Qingdao University, Qingdao, China. changsubmit@ 123456126.com
                Article
                S2212-8778(22)00022-9 101453
                10.1016/j.molmet.2022.101453
                8866070
                35121168
                e820b67f-66b1-404c-94f2-7313afda1040
                © 2022 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 8 December 2021
                : 22 January 2022
                : 28 January 2022
                Categories
                Review

                extracellular vesicles,diabetes,noncoding rna,exosomes
                extracellular vesicles, diabetes, noncoding rna, exosomes

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