Advances in mesenchymal stem cell exosomes: a review

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Abstract

Stem cells can be used for regenerative medicine and as treatments for disease. The application of tissue engineering-related transplantation, stem cells, and local changes in the microenvironment is expected to solve major medical problems. Currently, most studies focus on tissue repair and regeneration, and mesenchymal stem cells (MSCs) are among the most common research topics. MSCs are applicable as seed cells, and they represent one of the current hot topics in regenerative medicine research. However, due to storage limitations and because cell senescence occurs during in vitro expansion, their clinical application is challenging. Exosomes, which are secreted by MSCs through paracrine signalling, not only have the same effects as MSCs, but they also have the advantages of targeted delivery, low immunogenicity, and high repairability. This article reviews the acquisition methods, characteristics, biological functions, and clinical applications of exosomes.

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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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Biogenesis and secretion of exosomes.

Joanna Kowal, Mercedes Tkach, Clotilde Théry (2014)

Although observed for several decades, the release of membrane-enclosed vesicles by cells into their surrounding environment has been the subject of increasing interest in the past few years, which led to the creation, in 2012, of a scientific society dedicated to the subject: the International Society for Extracellular Vesicles. Convincing evidence that vesicles allow exchange of complex information fuelled this rise in interest. But it has also become clear that different types of secreted vesicles co-exist, with different intracellular origins and modes of formation, and thus probably different compositions and functions. Exosomes are one sub-type of secreted vesicles. They form inside eukaryotic cells in multivesicular compartments, and are secreted when these compartments fuse with the plasma membrane. Interestingly, different families of molecules have been shown to allow intracellular formation of exosomes and their subsequent secretion, which suggests that even among exosomes different sub-types exist. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Ceramide triggers budding of exosome vesicles into multivesicular endosomes.

Katarina Trajkovic, Chieh Hsu, Salvatore Chiantia … (2008)

Intraluminal vesicles of multivesicular endosomes are either sorted for cargo degradation into lysosomes or secreted as exosomes into the extracellular milieu. The mechanisms underlying the sorting of membrane into the different populations of intraluminal vesicles are unknown. Here, we find that cargo is segregated into distinct subdomains on the endosomal membrane and that the transfer of exosome-associated domains into the lumen of the endosome did not depend on the function of the ESCRT (endosomal sorting complex required for transport) machinery, but required the sphingolipid ceramide. Purified exosomes were enriched in ceramide, and the release of exosomes was reduced after the inhibition of neutral sphingomyelinases. These results establish a pathway in intraendosomal membrane transport and exosome formation.

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Author and article information

Contributors

Yaya Tang: 1253798483@qq.com

Yan Zhou: yanyan_850@163.com

Hong-Jun Li: lihj6912@hotmail.com

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 19 January 2021

Publication date PMC-release: 19 January 2021

Publication date Collection: 2021

Volume: 12

Electronic Location Identifier: 71

Affiliations

[1 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Key Laboratory of Vaccine Research and Development for Major Infectious Diseases of Yunnan Province, , Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, ; Kunming, 650118 People’s Republic of China

[2 ]GRID grid.285847.4, ISNI 0000 0000 9588 0960, Kunming Medical University, ; Kunming, 650500 People’s Republic of China

Article

Publisher ID: 2138

DOI: 10.1186/s13287-021-02138-7

PMC ID: 7814175

PubMed ID: 33468232

SO-VID: 5792e60f-032c-4c15-abec-780f3b8a83ed

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 18 August 2020

Date accepted : 4 January 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 31700154

Funded by: Chinese Academy of Medical Sciences Medicine and Health Technology Innovation Project

Award ID: 2016-I2M-3-026

Funded by: Major Science and Technology Special Project of Yunnan Province (Biomedicine)

Award ID: 2018ZF006

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ScienceOpen disciplines: Molecular medicine

Keywords: mesenchymal stem cells,exosomes,regenerative medicine,acquisition methods,biological characteristics,biological function,clinical application

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ScienceOpen disciplines: Molecular medicine

Keywords: mesenchymal stem cells, exosomes, regenerative medicine, acquisition methods, biological characteristics, biological function, clinical application

Advances in mesenchymal stem cell exosomes: a review

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Network and Systems Medicine

Most cited references 80

Extracellular vesicles: Exosomes, microvesicles, and friends

Biogenesis and secretion of exosomes.

Ceramide triggers budding of exosome vesicles into multivesicular endosomes.

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