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      Characteristics of culture-condition stimulated exosomes or their loaded hydrogels in comparison with other extracellular vesicles or MSC lysates

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          Abstract

          Recently, it has become popular to study the use of extracellular vesicles (EVs) secreted by stem cells to repair damaged tissues or lost cells. Various cell types and physiological fluids release EVs, and they play an important role in cell-to-cell communication. Moreover, EVs have been implicated in important processes, such as immune responses, homeostasis maintenance, coagulation, inflammation, cancer progression, angiogenesis, and antigen presentation. Thus, EVs participate in both physiological and pathological progression. The main classes of EVs include exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Exosomes, which carry a mass of signal molecules such as RNA, DNA, proteins, and lipids, are the most important of these EVs subsets. Currently, exosomes are generating substantial interest in the scientific community. Exosomes loaded hydrogels or under different cultural environments exhibit different properties and functions. Therefore, the exosomes obtained from different sources and conditions are worth reviewing. More importantly, no review article has compared the different EVs, such as exosomes, MVs, ApoBDs, and mesenchymal stem cell (MSC) lysates, which are special soluble substances. The differentiation between EVs and MSC lysates is a logical approach. Accordingly, this review provides an update on the latest progress in studying the roles of culture-condition stimulated exosomes or their loaded hydrogels and the differentiation between exosomes, MVs, ApoBDs, and MSC lysates. Published studies were retrieved from the PubMed® database for review.

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          Exosomes Facilitate Therapeutic Targeting of Oncogenic Kras in Pancreatic Cancer

          Sushrut Kamerkar, Valerie LeBleu, Hikaru Sugimoto … (2017)
          Summary The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes, extracellular vesicles generated by all cells, are naturally present in the blood. Here we demonstrate that enhanced retention of exosomes in circulation, compared to liposomes, is due to CD47 mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry siRNA or shRNA specific to oncogenic KRASG12D (iExosomes), a common mutation in pancreatic cancer. Compared to liposomes, iExosomes target oncogenic Kras with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. iExosomes treatment suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased their overall survival. Our results inform on a novel approach for direct and specific targeting of oncogenic Kras in tumors using iExosomes.
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            Oxidative Stress

            Helmut Sies, Carsten Berndt, Dean P. Jones … (2017)
            Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these converse properties. Redox balance is maintained by prevention, interception, and repair, and concomitantly the regulatory potential of molecular thiol-driven master switches such as Nrf2/Keap1 or NF-κB/IκB is used for system-wide oxidative stress response. Nonradical species such as hydrogen peroxide (H2O2) or singlet molecular oxygen, rather than free-radical species, perform major second messenger functions. Chemokine-controlled NADPH oxidases and metabolically controlled mitochondrial sources of H2O2 as well as glutathione- and thioredoxin-related pathways, with powerful enzymatic back-up systems, are responsible for fine-tuning physiological redox signaling. This makes for a rich research field spanning from biochemistry and cell biology into nutritional sciences, environmental medicine, and molecular knowledge-based redox medicine.
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              Hydrogels in regenerative medicine.

              Brandon V Slaughter, Shahana S Khurshid, Omar Z Fisher … (2009)
              Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Bioeng Biotechnol
                Journal ID (iso-abbrev): Front Bioeng Biotechnol
                Journal ID (publisher-id): Front. Bioeng. Biotechnol.
                Title: Frontiers in Bioengineering and Biotechnology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-4185
                Publication date (Electronic): 16 September 2022
                Publication date Collection: 2022
                Volume: 10
                Electronic Location Identifier: 1016833
                Affiliations
                [1] 1 Center of Regenerative Medicine and Department of Stomatology , Renmin Hospital of Wuhan University , Wuhan, China
                [2] 2 Department of Orthodontics , School and Hospital of Stomatology , Nanchang University , Nanchang, China
                [3] 3 Institute of Regenerative and Translational Medicine , Tianyou Hospital , Wuhan University of Science and Technology , Wuhan, China
                Author notes

                Edited by: Lihua Li, Jinan University, China

                Reviewed by: Yanfeng Han, Garvan Institute of Medical Research, Australia

                Harish Ramachandramoorthy, University of Texas at Arlington, United States

                *Correspondence: Qingsong Ye, qingsongye@ 123456whu.edu.cn ; Yan He, helen-1101@ 123456hotmail.com
                [ † ]

                These authors have contributed equally to this work and share first authorship

                This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                Publisher ID: 1016833
                DOI: 10.3389/fbioe.2022.1016833
                PMC ID: 9523448
                SO-VID: 92960324-67b0-4464-aef9-886ba3d97dd8
                Copyright © Copyright © 2022 Luo, Li, Wang, Wang, Duan, Li, Peng, Ye and He.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 11 August 2022
                Date accepted : 05 September 2022
                Categories
                Subject: Bioengineering and Biotechnology
                Subject: Review

                Keywords: extracellular vesicles,exosomes,exosomes loaded hydrogels,microvesicles,apoptotic bodies,mesenchymal stem cell lysates
                Data availability:
                Keywords: extracellular vesicles, exosomes, exosomes loaded hydrogels, microvesicles, apoptotic bodies, mesenchymal stem cell lysates

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