Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency

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Abstract

Extracellular vesicles (EVs) have the innate ability to carry proteins, lipids, and nucleic acids between cells, and thus these vesicles have gained much attention as potential therapeutic delivery vehicles. Many strategies have been explored to enhance the loading of specific cargoes of interest into EVs, which could result in the delivery of more therapeutic to recipient cells, thus enhancing therapeutic efficacy. In this review, we discuss the natural biogenesis of EVs, the mechanism by which proteins and nucleic acids are selected for inclusion in EVs, and novel methods that have been employed to enhance loading of specific cargoes into EVs. As well, we discuss biodistribution of administered EVs in vivo and summarize clinical trials that have attempted to harness the therapeutic potential of EVs.

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Abstract

Parks and René have reviewed extracellular vesicle (EV) biogenesis and cargo loading, methods for enhancing loading of specific cargo into EVs, biodistribution of administered EVs, and clinical trials that have harnessed the therapeutic potential of EVs.

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Most cited references 183

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Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

M Dominici, K Le Blanc, I. Mueller … (2006)

The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.

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Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)

Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).

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Extracellular vesicles: Exosomes, microvesicles, and friends

Graça Raposo, Willem Stoorvogel (2013)

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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Author and article information

Contributors

Robin J. Parks

Journal

Journal ID (nlm-ta): Mol Ther Methods Clin Dev

Journal ID (iso-abbrev): Mol Ther Methods Clin Dev

Title: Molecular Therapy. Methods & Clinical Development

Publisher: American Society of Gene & Cell Therapy

ISSN (Electronic): 2329-0501

Publication date PMC-release: 26 April 2024

Publication date Collection: 13 June 2024

Publication date (Electronic): 26 April 2024

Volume: 32

Issue: 2

Electronic Location Identifier: 101259

Affiliations

[1 ]Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada

[2 ]Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada

[3 ]Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1H 8M5, Canada

[4 ]Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON K1H 8L6, Canada

Author notes

[∗ ]Corresponding author: Robin J. Parks, Ottawa Hospital Research Institute, Room C4415 - Regenerative Medicine Program, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada. rparks@ 123456ohri.ca

Article

Publisher Item ID: S2329-0501(24)00075-5 Publisher ID: 101259

DOI: 10.1016/j.omtm.2024.101259

PMC ID: 11103572

PubMed ID: 38770107

SO-VID: bee1898f-cb43-42c6-97c0-d45cedfe8b3b

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency

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Bacterial extracellular vesicles

Most cited references 183

Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Extracellular vesicles: Exosomes, microvesicles, and friends

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