25
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The role of extracellular vesicles in biomineralisation: current perspective and application in regenerative medicine

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Extracellular vesicles comprise a heterogenous population of exosomes and microvesicles that have critical roles in intercellular signalling and tissue development. These complex particles have been implicated as mediators of the therapeutic effects of stem cells via the transfer of an assorted cargo of proteins and nucleic acids, which can modulate inflammation and enhance endogenous regeneration in a range of tissues. In addition, extracellular vesicles have the capacity to be loaded with therapeutic molecules for targeted delivery of pharmaceuticals. The versatility, biostability and biocompatibility of extracellular vesicles make them appealing for regenerative medicine and may endow considerable advantages over single molecule approaches. Furthermore, since production can be optimised and assessed ex vivo, extracellular vesicles present a decreased risk of neoplastic transformation when compared with cell-based methods. To date, the contribution of vesicles to tissue development has perhaps been most comprehensively defined within hard tissues, such as endochondral bone, where they were first identified in 1969 and henceforth referred to as matrix vesicles. Within developing bone, vesicles function as vehicles for the delivery of pro-osteogenic factors and initiate early nucleational events necessary for matrix mineralisation. However, advancement in our understanding of the biogenesis and characterisation of matrix vesicles has occurred largely in parallel to associated developments in wider extracellular vesicle biology. As such, there is a requirement to align current understanding of matrix vesicle–mediated mineralisation within the context of an evolving literature surrounding exosomes and microvesicles. In this review, we present an overview of current progress and opinion surrounding the application of vesicles in regenerative medicine with a primary focus on their potential as an acellular approach for enhancing hard tissue regeneration. This is balanced with an assessment of areas where further development is required to maximise their application for regenerative medicine.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo

          Emerging evidence suggests that extracellular vesicles (EVs) are secreted by diverse tissues and play important roles in cell-cell communication, organ interactions and tissue homeostasis. Studies have reported the use of EVs to stimulate tissue regeneration, such as hepatic cell regeneration, and to treat diseases, such as pulmonary hypertension. However, little is known about the osteogenic effect of EVs. In this study, we explore the role of bone marrow stromal cell-derived EVs in the regulation of osteoblast activity and bone regeneration. We isolated bone marrow stromal/stem cell (BMSC)-derived EVs through gradient ultracentrifugation and ultrafiltration, and tested the influence of the EVs on osteogenesis both in vivo and in vitro. The results indicated that EVs positively regulated osteogenic genes and osteoblastic differentiation but did not inhibit proliferation in vitro. Furthermore, we constructed an EVs delivery system to stimulate bone formation in Sprague Dawley (SD) rats with calvarial defects. We found that BMSC-derived EVs led to more bone formation in the critical-size calvarial bone defects. Moreover, we found that miR-196a plays an essential role in the regulation of osteoblastic differentiation and the expression of osteogenic genes. We anticipate that our assay using bone marrow stromal cell-derived EVs will become a valuable tool for promoting bone regeneration.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes Promotes Bone Regeneration

            Gang Wu (2018)
            Exosomes, nanoscale extracellular vesicles functioning as cell-to-cell communicators, are an emerging promising therapeutic in the field of bone tissue engineering. Here, we report the construction and evaluation of a novel cell-free tissue-engineered bone that successfully accelerated the restoration of critical-sized mouse calvarial defects through combining exosomes derived from human adipose-derived stem cells (hASCs) with poly(lactic-co-glycolic acid) (PLGA) scaffolds. The exosomes were immobilized on the polydopamine-coating PLGA (PLGA/pDA) scaffolds under mild chemical conditions. Specifically, we investigated the effects of hASC-derived exosomes on the osteogenic, proliferation, and migration capabilities of human bone marrow-derived mesenchymal stem cells in vitro and optimized their osteoinductive effects through osteogenic induction. Furthermore, an in vitro assay showed exosomes could release from PLGA/pDA scaffold slowly and consistently and in vivo results showed this cell-free system enhanced bone regeneration significantly, at least partially through its osteoinductive effects and capacities of promoting mesenchymal stem cells migration and homing in the newly formed bone tissue. Therefore, overall results demonstrated that our novel cell-free system comprised of hASC-derived exosomes and PLGA/pDA scaffold provides a new therapeutic paradigm for bone tissue engineering and showed promising potential in repairing bone defects.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro

              Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and disability with no effective treatment available. Recently, allogeneic human mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy for OA. Increasing evidence suggests that therapeutic efficacy of MSC depends on paracrine signalling. Here we investigated the role of extracellular vesicles (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage repair. Methods: To test the effect of BMMSC-EVs on OA cartilage inflammation, TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC-EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h. To assess the impact of BMMSC-EVs on cartilage regeneration, BMMSC-EVs were added to the regeneration cultures of human OA chondrocytes, which were analyzed after 4 weeks for glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay. Furthermore, paraffin sections of the regenerated tissue were stained for proteoglycans (safranin-O) and type II collagen (immunostaining). Results: We show that BMMSC-EVs inhibit the adverse effects of inflammatory mediators on cartilage homeostasis. When co-cultured with OA chondrocytes, BMMSC-EVs abrogated the TNF-alpha-mediated upregulation of COX2 and pro-inflammatory interleukins and inhibited TNF-alpha-induced collagenase activity. BMMSC-EVs also promoted cartilage regeneration in vitro. Addition of BMMSC-EVs to cultures of chondrocytes isolated from OA patients stimulated production of proteoglycans and type II collagen by these cells. Conclusion: Our data demonstrate that BMMSC-EVs can be important mediators of cartilage repair and hold great promise as a novel therapeutic for cartilage regeneration and osteoarthritis.
                Bookmark

                Author and article information

                Journal
                J Tissue Eng
                J Tissue Eng
                TEJ
                sptej
                Journal of Tissue Engineering
                SAGE Publications (Sage UK: London, England )
                2041-7314
                02 November 2018
                Jan-Dec 2018
                : 9
                : 2041731418810130
                Affiliations
                [1 ]School of Chemical Engineering, University of Birmingham, Birmingham, UK
                [2 ]School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
                Author notes
                [*]Owen Gareth Davies, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, Leicestershire, UK. Email: O.G.Davies@ 123456lboro.ac.uk
                Author information
                https://orcid.org/0000-0001-5953-1808
                Article
                10.1177_2041731418810130
                10.1177/2041731418810130
                6236483
                30450187
                fbe9d94e-4bbd-46d0-a179-457d644c23c5
                © The Author(s) 2018

                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
                : 25 July 2018
                : 9 October 2018
                Funding
                Funded by: Engineering and Physical Sciences Research Council, FundRef https://doi.org/10.13039/501100000266;
                Categories
                Acellular Approaches for Regenerative Medicine: Driving Biology without the Cell
                Custom metadata
                January-December 2018

                Biomedical engineering
                extracellular vesicles,exosomes,mineralisation,matrix vesicles,pathological calcification,regenerative medicine

                Comments

                Comment on this article