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      Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

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          Abstract

          Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane vesicles derived from most cell types. Carrying diverse biomolecules from their parent cells, EVs are important mediators of intercellular communication and thus play significant roles in physiological and pathological processes. Owing to their natural biogenesis process, EVs are generated with high biocompatibility, enhanced stability, and limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic delivery vehicles. EVs have been reported to be used for the delivery of siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, and CRISPR/Cas9 in the treatment of various diseases. As a natural drug delivery vectors, EVs can penetrate into the tissues and be bioengineered to enhance the targetability. Although EVs’ characteristics make them ideal for drug delivery, EV-based drug delivery remains challenging, due to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS.

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          Most cited references112

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          ExoCarta: A Web-Based Compendium of Exosomal Cargo.

          Exosomes are membranous vesicles that are released by a variety of cells into the extracellular microenvironment and are implicated in intercellular communication. As exosomes contain RNA, proteins and lipids, there is a significant interest in characterizing the molecular cargo of exosomes. Here, we describe ExoCarta (http://www.exocarta.org), a manually curated Web-based compendium of exosomal proteins, RNAs and lipids. Since its inception, the database has been highly accessed (>54,000 visitors from 135 countries). The current version of ExoCarta hosts 41,860 proteins, >7540 RNA and 1116 lipid molecules from more than 286 exosomal studies annotated with International Society for Extracellular Vesicles minimal experimental requirements for definition of extracellular vesicles. Besides, ExoCarta features dynamic protein-protein interaction networks and biological pathways of exosomal proteins. Users can download most often identified exosomal proteins based on the number of studies. The downloaded files can further be imported directly into FunRich (http://www.funrich.org) tool for additional functional enrichment and interaction network analysis.
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            Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine.

            To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.
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              Decisions about dendritic cells: past, present, and future.

              A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of antigens in situ and new approaches to vaccine design in preclinical and clinical systems.
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                Author and article information

                Journal
                Drug Deliv
                Drug Deliv
                IDRD
                idrd20
                Drug Delivery
                Taylor & Francis
                1071-7544
                1521-0464
                2020
                08 April 2020
                : 27
                : 1
                : 585-598
                Affiliations
                Department of Stomatology, Sichuan Cancer Hospital, Sichuan Key Laboratory of Radiation Oncology, School of Medicine, University of Electronic Science and Technology of China , Chengdu, PR China
                Author notes
                Guiquan Zhu zgq@ 123456sichuancancer.org Department of Stomatology, School of Medicine, Sichuan Cancer Hospital, Sichuan Key Laboratory of Radiation Oncology, University of Electronic Science and Technology of China , No. 55, Section 4, Renmin South Road, Chengdu, Sichuan 610041, PR China
                Article
                1748758
                10.1080/10717544.2020.1748758
                7178886
                32264719
                b56fc872-22c8-419b-b8c1-6e9ba3bb8f51
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 November 2019
                : 18 March 2020
                : 25 March 2020
                Page count
                Figures: 2, Tables: 2, Pages: 14, Words: 13675
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81672690
                Award ID: 81772900
                Award ID: 81872196
                Award ID: 81972541
                Funded by: Department of Science and Technology of Sichuan Province 10.13039/501100004829
                Award ID: 2018JY0646
                This work was supported by the National Natural Science Foundation of China [Grant Nos. 81672690, 81772900, 81872196, and 81972541] and the Department of Science and Technology of Sichuan Province [Grant No. 2018JY0646].
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                drug delivery,extracellular vesicles,exosomes,microvesicles

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