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      Exosomes and Their Bioengineering Strategies in the Cutaneous Wound Healing and Related Complications: Current Knowledge and Future Perspectives

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          Abstract

          Exosomes, as therapeutically relevant cell-secreted extracellular vesicles, have attracted enormous interest because they participate in intercellular communication and facilitate wound healing. Stem cell-derived exosomes exhibit similar biological effects to source cells with the exception of low immunogenicity and no tumorigenicity, as well as superior efficacy in promoting wound healing. Exosomes accelerate wound healing by promoting angiogenesis and cell proliferation, as well as balancing inflammatory responses. Particularly, when exosomes are genetically modified or used in combination with materials, they can exhibit better comprehensive therapeutic properties, such as enriching active ingredients, targeted delivery, and physiological barrier to penetration, which are not available in traditional single products. Besides, exosomes have also been considered for diagnostic and therapeutic uses related to wounds, such as repairing complex wounds, enhancing graft success, treating related complications, and serving as diagnostic biomarkers. However, their clinical applications still face challenges, as reliable commercial products are not yet available. This review will focus on recent research advances that describe the characteristics and isolation of exosomes, introduce the sources of exosomes suitable for wound repair and related complications, illustrate the value of engineered exosomes and their development directions in the future, and provide evidence for the potential therapeutic application of exosomes in wound healing, as well as discuss potential risks, challenges, and solutions for future applications.

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          Most cited references235

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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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            Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

            Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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              Extracellular vesicles: Exosomes, microvesicles, and friends

              Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
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                Author and article information

                Journal
                Int J Biol Sci
                Int J Biol Sci
                ijbs
                International Journal of Biological Sciences
                Ivyspring International Publisher (Sydney )
                1449-2288
                2023
                27 February 2023
                : 19
                : 5
                : 1430-1454
                Affiliations
                [1 ]Department of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
                [2 ]Division of Nephrology, Peking University Shenzhen Hospital, Peking University, Shenzhen 518036, China.
                [3 ]Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen 518060, China.
                [4 ]College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, China.
                [5 ]Human Histology & Embryology Section, Department of Surgery, Dentistry, Pediatrics & Gynecology, University of Verona Medical School, Verona 37134, Italy.
                Author notes
                ✉ Corresponding author: Jun Wu, junwupro@ 123456126.com .

                * Contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijbsv19p1430
                10.7150/ijbs.80430
                10086759
                37056923
                97ace5c9-0980-45b1-a141-4641c16f6f76
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 2 November 2022
                : 30 January 2023
                Categories
                Review

                Life sciences
                exosomes,stem cells,engineered exosomes,wound healing,biomaterials,complex wounds,complications,biomarkers.

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