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      Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

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          Abstract

          Osteoporosis is a chronic disease requiring long-term, sometimes lifelong, management. With the aging population, the prevalence of osteoporosis is increasing, and with it so is the risk of hip fracture and subsequent poor quality of life and higher mortality. Current therapies for osteoporosis have various significant side effects limiting patient compliance and use. Recent evidence has demonstrated the significant role of exosomes in osteoporosis both in vivo and in vitro. In this review, we summarize the pathogenesis of senile osteoporosis, highlight the properties and advantages of exosomes, and explore the recent literature on the use of exosomes in osteogenesis regulation. This is a very helpful review as several exosomes-based therapeutics have recently entered clinical trials for non-skeletal applications, such as pancreatic cancer, renal transplantation, and therefore it is urgent for bone researchers to explore whether exosomes can become the next class of orthobiologics for the treatment of osteoporosis.

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          Most cited references84

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          MicroRNAs: genomics, biogenesis, mechanism, and function.

          MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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            Extracellular vesicles: biology and emerging therapeutic opportunities.

            Within the past decade, extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells in both prokaryotes and higher eukaryotes to regulate a diverse range of biological processes. In addition, pathophysiological roles for extracellular vesicles are beginning to be recognized in diseases including cancer, infectious diseases and neurodegenerative disorders, highlighting potential novel targets for therapeutic intervention. Moreover, both unmodified and engineered extracellular vesicles are likely to have applications in macromolecular drug delivery. Here, we review recent progress in understanding extracellular vesicle biology and the role of extracellular vesicles in disease, discuss emerging therapeutic opportunities and consider the associated challenges.
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              Exosomes Facilitate Therapeutic Targeting of Oncogenic Kras in Pancreatic Cancer

              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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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                23 October 2020
                2020
                : 8
                : 594247
                Affiliations
                [1] 1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [2] 2Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA, United States
                Author notes

                Edited by: Gang Liu, Xiamen University, China

                Reviewed by: Junqing Wang, Sun Yat-sen University, China; Luciana Dini, Sapienza University of Rome, Italy

                *Correspondence: Guohui Liu, liuguohui@ 123456hust.edu.cn

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

                Article
                10.3389/fbioe.2020.594247
                7644826
                33195163
                76c2123e-0056-43bd-97e3-39fee2a1f496
                Copyright © 2020 Xie, Xiong, Panayi, Hu, Zhou, Xue, Lin, Chen, Yan, Mi and Liu.

                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
                : 12 August 2020
                : 06 October 2020
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 84, Pages: 10, Words: 0
                Categories
                Bioengineering and Biotechnology
                Review

                osteoporosis,exosomes,mesenchymal stem cells (mscs),osteoblasts,osteoclasts

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