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      The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles

      review-article
      Author(s): , *
      Publication date (Electronic):
      Journal: Nutrients
      Publisher: MDPI
      Keywords: extracellular vesicle, exosome, necrotizing enterocolitis, breast milk

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          Abstract

          In the past few decades, interest in the therapeutic benefits of exosomes and extracellular vesicles (EVs) has grown exponentially. Exosomes/EVs are small particles which are produced and exocytosed by cells throughout the body. They are loaded with active regulatory and stimulatory molecules from the parent cell including miRNAs and enzymes, making them prime targets in therapeutics and diagnostics. Breast milk, known for years to have beneficial health effects, contains a population of EVs which may mediate its therapeutic effects. This review offers an update on the therapeutic potential of exosomes/EVs in disease, with a focus on EVs present in human breast milk and their remedial effect in the gastrointestinal disease necrotizing enterocolitis. Additionally, the relationship between EV miRNAs, health, and disease will be examined, along with the potential for EVs and their miRNAs to be engineered for targeted treatments.

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          Most cited references81

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          Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes

          K. Teng, M Adam Mahmood, C Wu … (1985)
          Using ferritin-labeled protein A and colloidal gold-labeled anti-rabbit IgG, the fate of the sheep transferrin receptor has been followed microscopically during reticulocyte maturation in vitro. After a few minutes of incubation at 37 degrees C, the receptor is found on the cell surface or in simple vesicles of 100-200 nm, in which the receptor appears to line the limiting membrane of the vesicles. With time (60 min or longer), large multivesicular elements (MVEs) appear whose diameter may reach 1-1.5 micron. Inside these large MVEs are round bodies of approximately 50-nm diam that bear the receptor at their external surfaces. The limiting membrane of the large MVEs is relatively free from receptor. When the large MVEs fuse with the plasma membrane, their contents, the 50-nm bodies, are released into the medium. The 50-nm bodies appear to arise by budding from the limiting membrane of the intracellular vesicles. Removal of surface receptor with pronase does not prevent exocytosis of internalized receptor. It is proposed that the exocytosis of the approximately 50-nm bodies represents the mechanism by which the transferrin receptor is shed during reticulocyte maturation.
          Article 0 comments Cited 445 times – based on 0 reviews     Review now
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            Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.

            J Escola, M Kleijmeer, W Stoorvogel … (1998)
            Association of major histocompatibility complex (MHC) class II molecules with peptides occurs in a series of endocytic vacuoles, termed MHC class II-enriched compartments (MIICs). Morphological criteria have defined several types of MIICs, including multivesicular MIICs, which are composed of 50-60-nm vesicles surrounded by a limiting membrane. Multivesicular MIICs can fuse with the plasma membrane, thereby releasing their internal vesicles into the extracellular space. The externalized vesicles, termed exosomes, carry MHC class II and can stimulate T-cells in vitro. In this study, we show that exosomes are enriched in the co-stimulatory molecule CD86 and in several tetraspan proteins, including CD37, CD53, CD63, CD81, and CD82. Interestingly, subcellular localization of these molecules revealed that they were concentrated on the internal membranes of multivesicular MIICs. In contrast to the tetraspans, other membrane proteins of MIICs, such as HLA-DM, Lamp-1, and Lamp-2, were mainly localized to the limiting membrane and were hardly detectable on the internal membranes of MIICs nor on exosomes. Because internal vesicles of multivesicular MIICs are thought to originate from inward budding of the limiting membrane, the differential distribution of membrane proteins on the internal and limiting membranes of MIICs has to be driven by active protein sorting.
            Article 0 comments Cited 377 times – based on 0 reviews     Review now
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              Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth.

              Hongqi Xin, Yi Li, Ben Buller … (2012)
              Multipotent mesenchymal stromal cells (MSCs) have potential therapeutic benefit for the treatment of neurological diseases and injury. MSCs interact with and alter brain parenchymal cells by direct cell-cell communication and/or by indirect secretion of factors and thereby promote functional recovery. In this study, we found that MSC treatment of rats subjected to middle cerebral artery occlusion (MCAo) significantly increased microRNA 133b (miR-133b) level in the ipsilateral hemisphere. In vitro, miR-133b levels in MSCs and in their exosomes increased after MSCs were exposed to ipsilateral ischemic tissue extracts from rats subjected to MCAo. miR-133b levels were also increased in primary cultured neurons and astrocytes treated with the exosome-enriched fractions released from these MSCs. Knockdown of miR-133b in MSCs confirmed that the increased miR-133b level in astrocytes is attributed to their transfer from MSCs. Further verification of this exosome-mediated intercellular communication was performed using a cel-miR-67 luciferase reporter system and an MSC-astrocyte coculture model. Cel-miR-67 in MSCs was transferred to astrocytes via exosomes between 50 and 100 nm in diameter. Our data suggest that the cel-miR-67 released from MSCs was primarily contained in exosomes. A gap junction intercellular communication inhibitor arrested the exosomal microRNA communication by inhibiting exosome release. Cultured neurons treated with exosome-enriched fractions from MSCs exposed to 72 hours post-MCAo brain extracts significantly increased the neurite branch number and total neurite length. This study provides the first demonstration that MSCs communicate with brain parenchymal cells and may regulate neurite outgrowth by transfer of miR-133b to neural cells via exosomes. Copyright © 2012 AlphaMed Press.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nutrients
                Journal ID (iso-abbrev): Nutrients
                Journal ID (publisher-id): nutrients
                Title: Nutrients
                Publisher: MDPI
                ISSN (Electronic): 2072-6643
                Publication date (Electronic): 11 March 2020
                Publication date Collection: March 2020
                Volume: 12
                Issue: 3
                Electronic Location Identifier: 745
                Affiliations
                Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Department of Pediatric Surgery, Nationwide Children’s Hospital, Columbus, OH 43205, USA; jeffrey.galley@ 123456nationwidechildrens.org
                Author notes
                [* ]Correspondence: gail.besner@ 123456nationwidechildrens.org ; Tel.: +1-614-722-3900
                Article
                Publisher ID: nutrients-12-00745
                DOI: 10.3390/nu12030745
                PMC ID: 7146576
                PubMed ID: 32168961
                SO-VID: be866b5d-5cf5-4202-8f04-a1e455ba8c53
                Copyright © © 2020 by the authors.
                License:

                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
                Date received : 09 January 2020
                Date accepted : 08 March 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: extracellular vesicle,exosome,necrotizing enterocolitis,breast milk
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: extracellular vesicle, exosome, necrotizing enterocolitis, breast milk

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