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      The Current Trends in Using Nanoparticles, Liposomes, and Exosomes for Semen Cryopreservation

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          Abstract

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          Long-term preservation of semen is a pivotal step for artificial insemination in most farm animal species, but it is associated with cellular insults at the cell membrane and cytoskeleton level as well as the generation of reactive oxygen species (ROS). We highlight the recent strategies to combat these negative effects through defending against the ROS via antioxidant nanoparticles or through repairing/regenerating the damaged sperm through using liposomes and most recently exosomes derived from the reproductive tract or stem cells.

          Abstract

          Cryopreservation is an essential tool to preserve sperm cells for zootechnical management and artificial insemination purposes. Cryopreservation is associated with sperm damage via different levels of plasma membrane injury and oxidative stress. Nanoparticles are often used to defend against free radicals and oxidative stress generated through the entire process of cryopreservation. Recently, artificial or natural nanovesicles including liposomes and exosomes, respectively, have shown regenerative capabilities to repair damaged sperm during the freeze–thaw process. Exosomes possess a potential pleiotropic effect because they contain antioxidants, lipids, and other bioactive molecules regulating and repairing spermatozoa. In this review, we highlight the current strategies of using nanoparticles and nanovesicles (liposomes and exosomes) to combat the cryoinjuries associated with semen cryopreservation.

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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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            Toxic potential of materials at the nanolevel.

            Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.
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              Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial

              Background DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. Patients and methods Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules) or peptides (10 versus 100 μg/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. Results The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. Conclusion The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.
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                Author and article information

                Journal
                Animals (Basel)
                Animals (Basel)
                animals
                Animals : an Open Access Journal from MDPI
                MDPI
                2076-2615
                03 December 2020
                December 2020
                : 10
                : 12
                : 2281
                Affiliations
                [1 ]Department of Animal Production, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia
                [2 ]Department of Comparative Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
                [3 ]Department of Animal Production, Faculty of Agriculture, Mansoura University, Mansoura 35516, Egypt; w-khalil@ 123456mans.edu.eg
                [4 ]Department of Biochemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia; mgalharbi@ 123456ksu.edu.sa
                [5 ]Center for Reproductive Sciences, Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, CA 94143, USA
                Author notes
                Author information
                https://orcid.org/0000-0002-7633-730X
                https://orcid.org/0000-0001-9539-3246
                https://orcid.org/0000-0002-4656-1618
                Article
                animals-10-02281
                10.3390/ani10122281
                7761754
                33287256
                3de8e8c7-1208-4b8c-948c-7bf75b7825f4
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 November 2020
                : 02 December 2020
                Categories
                Review

                nanoparticles,liposomes,exosomes,semen,cryopreservation,livestock production

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