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      MSC-Derived Exosomes-Based Therapy for Peripheral Nerve Injury: A Novel Therapeutic Strategy

      , , , , ,
      BioMed Research International

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          Although significant advances have been made in synthetic nerve conduits and surgical techniques, complete regeneration following peripheral nerve injury (PNI) remains far from optimized. The repair of PNI is a highly heterogeneous process involving changes in Schwann cell phenotypes, the activation of macrophages, and the reconstruction of the vascular network. At present, the efficacy of MSC-based therapeutic strategies for PNI can be attributed to paracrine secretion. Exosomes, as a product of paracrine secretion, are considered to be an important regulatory mediator. Furthermore, accumulating evidence has demonstrated that exosomes from mesenchymal stem cells (MSCs) can shuttle bioactive components (proteins, lipids, mRNA, miRNA, lncRNA, circRNA, and DNA) that participate in almost all of the abovementioned processes. Thus, MSC exosomes may represent a novel therapeutic tool for PNI. In this review, we discuss the current understanding of MSC exosomes related to peripheral nerve repair and provide insights for developing a cell-free MSC therapeutic strategy for PNI.

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          Biogenesis and secretion of exosomes.

          Although observed for several decades, the release of membrane-enclosed vesicles by cells into their surrounding environment has been the subject of increasing interest in the past few years, which led to the creation, in 2012, of a scientific society dedicated to the subject: the International Society for Extracellular Vesicles. Convincing evidence that vesicles allow exchange of complex information fuelled this rise in interest. But it has also become clear that different types of secreted vesicles co-exist, with different intracellular origins and modes of formation, and thus probably different compositions and functions. Exosomes are one sub-type of secreted vesicles. They form inside eukaryotic cells in multivesicular compartments, and are secreted when these compartments fuse with the plasma membrane. Interestingly, different families of molecules have been shown to allow intracellular formation of exosomes and their subsequent secretion, which suggests that even among exosomes different sub-types exist. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views.

            Mesenchymal stem cells or multipotent stromal cells (MSCs) isolated from the bone marrow of adult organisms were initially characterized as plastic adherent, fibroblastoid cells with the capacity to generate heterotopic osseous tissue when transplanted in vivo. In recent years, MSCs or MSC-like cells have been shown to reside within the connective tissue of most organs, and their surface phenotype has been well described. A large number of reports have also indicated that the cells possess the capacity to transdifferentiate into epithelial cells and lineages derived from the neuroectoderm. The broad developmental plasticity of MSCs was originally thought to contribute to their demonstrated efficacy in a wide variety of experimental animal models of disease as well as in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for transdifferentiation in tissue repair. Herein, we critically evaluate the literature describing the plasticity of MSCs and offer insight into how the molecular and functional heterogeneity of this cell population, which reflects the complexity of marrow stroma as an organ system, may confound interpretation of their transdifferentiation potential. Additionally, we argue that this heterogeneity also provides a basis for the broad therapeutic efficacy of MSCs.
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              Exosome secretion: molecular mechanisms and roles in immune responses.

              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.

                Author and article information

                Biomed Res Int
                Biomed Res Int
                BioMed Research International
                18 August 2019
                : 2019
                : 6458237
                College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471023, China
                Author notes

                Guest Editor: Shi-Cong Tao

                Author information
                Copyright © 2019 Ruiqi Dong et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 9 April 2019
                : 6 July 2019
                : 25 July 2019
                Funded by: National Natural Science Foundation of China
                Award ID: U1504325
                Funded by: Henan Provincial for Higher Education Key Research Project Plan
                Award ID: 19B230005
                Review Article


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