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      Adipose stem cells-released extracellular vesicles as a next-generation cargo delivery vehicles: a survey of minimal information implementation, mass production and functional modification

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          Abstract

          Objectives

          To investigate current situation of minimal information implementation highlighted by minimal information for studies of extracellular vesicles 2018 (MISEV2018) guidelines, and explore technological advances towards mass production and functional modification in aesthetic, plastic and reconstructive surgery.

          Methods

          Original articles on extracellular vesicles (EVs) of adipose stem cells (ASCs) were identified. Statistics upon minimal information for EVs research, such as species, cell types, culture conditions, conditioned media harvesting parameters, EVs isolation/storage/identification/quantification, functional uptake and working concentration, were analyzed.

          Results

          The items of cell culture conditions such as passage number, seeding density, conditioned media harvesting time, functional uptake and working concentration were poorly documented, with a reporting percentage of 47.13%, 54.02%, 29.89%, 62.07% and 36.21%, respectively. However, there were some studies not reporting information of ASCs origin, culture medium, serum, EVs isolation methods, quantification and identification of EVs, accounting for 3.45%, 10.34%, 6.90%, 3.45%, 18.39% and 4.02%, respectively. Serum deprivation and trophic factors stimuli were attempted for EVs mass production. Several technological advances towards functional modification included hypoxia pre-condition, engineering EVs and controlled release. Presently, ASCs EVs have been applied in multiple fields, including diabetic/non-diabetic wound healing, angiogenesis, inflammation modulation, fat grafting, hair regeneration, antiaging, and healing and regeneration of cartilage/bone/peripheral nerve/tendon.

          Conclusion

          Our results highlight normative reporting of ASCs EVs in functional studies to increase reliability and reproducibility of scientific publications. The advances towards mass production and functional modification of ASCs EVs are also recommended to enhance therapeutic effects.

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          Most cited references188

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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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            Extracellular vesicles as a next-generation drug delivery platform

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              Engineering Bioactive Self-Healing Antibacterial Exosomes Hydrogel for Promoting Chronic Diabetic Wound Healing and Complete Skin Regeneration

              Rationale: Chronic nonhealing diabetic wound therapy and complete skin regeneration remains a critical clinical challenge. The controlled release of bioactive factors from a multifunctional hydrogel was a promising strategy to repair chronic wounds. Methods: Herein, for the first time, we developed an injectable, self-healing and antibacterial polypeptide-based FHE hydrogel (F127/OHA-EPL) with stimuli-responsive adipose-derived mesenchymal stem cells exosomes (AMSCs-exo) release for synergistically enhancing chronic wound healing and complete skin regeneration. The materials characterization, antibacterial activity, stimulated cellular behavior and in vivo full-thickness diabetic wound healing ability of the hydrogels were performed and analyzed. Results: The FHE hydrogel possessed multifunctional properties including fast self-healing process, shear-thinning injectable ability, efficient antibacterial activity, and long term pH-responsive bioactive exosomes release behavior. In vitro, the FHE@exosomes (FHE@exo) hydrogel significantly promoted the proliferation, migration and tube formation ability of human umbilical vein endothelial cells (HUVECs). In vivo, the FHE@exo hydrogel significantly enhanced the healing efficiency of diabetic full-thickness cutaneous wounds, characterized with enhanced wound closure rates, fast angiogenesis, re-epithelization and collagen deposition within the wound site. Moreover, the FHE@exo hydrogel displayed better healing outcomes than those of exosomes or FHE hydrogel alone, suggesting that the sustained release of exosomes and FHE hydrogel can synergistically facilitate diabetic wound healing. Skin appendages and less scar tissue also appeared in FHE@exo hydrogel treated wounds, indicating its potent ability to achieve complete skin regeneration. Conclusion: This work offers a new approach for repairing chronic wounds completely through a multifunctional hydrogel with controlled exosomes release.
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                Author and article information

                Contributors
                jianghypsh@163.com
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                3 May 2022
                3 May 2022
                2022
                : 13
                : 182
                Affiliations
                GRID grid.506261.6, ISNI 0000 0001 0706 7839, Plastic Surgery Hospital, , Chinese Academy of Medical Sciences and Peking Union Medical College, ; 33 Badachu Road, Shijingshan District, Beijing, 100144 People’s Republic of China
                Author information
                http://orcid.org/0000-0002-3948-372X
                Article
                2849
                10.1186/s13287-022-02849-5
                9062865
                34998430
                d50fbc85-dfef-4044-922c-8594e67d757f
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 29 November 2021
                : 12 April 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002418, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College;
                Award ID: 2017-12M-1-007
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Molecular medicine
                adipose stem cells,extracellular vesicles,functional modification,mass production,minimal information,misev2018 guidelines

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