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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2020; 12(12): 1529-1552
Published online Dec 26, 2020. doi: 10.4252/wjsc.v12.i12.1529
Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine
Alberto González-González, Daniel García-Sánchez, Monica Dotta, José C Rodríguez-Rey, Flor M Pérez-Campo
Alberto González-González, Daniel García-Sánchez, Monica Dotta, José C Rodríguez-Rey, Flor M Pérez-Campo, Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Santander 39011, Cantabria, Spain
Author contributions: González-González A, García-Sánchez D, Dotta M, Rodríguez-Rey JC, and Pérez-Campo FM wrote and approved the final version of the manuscript.
Supported by Spanish Ministerio de Economía y Competitividad, No. RTI2018-097324; Pre-doctoral program in Biomedicine from the University of Cantabria and the Instituto de Investigación Valdecilla (IDIVAL), No. PREVAL 19/02 and PREVAL 20/01.
Conflict-of-interest statement: None of the authors have any conflicts of interest relevant to this study.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Flor M Pérez-Campo, BSc, MSc, PhD, Assistant Professor, Senior Scientist, Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Avda Cardenal Herrera Oria S/N, Santander 39011, Cantabria, Spain. f.perezcampo@unican.es
Received: June 29, 2020
Peer-review started: June 29, 2020
First decision: September 24, 2020
Revised: October 7, 2020
Accepted: November 11, 2020
Article in press: November 11, 2020
Published online: December 26, 2020
Processing time: 180 Days and 8 Hours
Abstract

Mesenchymal stem cells (MSCs) are the most frequently used stem cells in clinical trials due to their easy isolation from various adult tissues, their ability of homing to injury sites and their potential to differentiate into multiple cell types. However, the realization that the beneficial effect of MSCs relies mainly on their paracrine action, rather than on their engraftment in the recipient tissue and subsequent differentiation, has opened the way to cell-free therapeutic strategies in regenerative medicine. All the soluble factors and vesicles secreted by MSCs are commonly known as secretome. MSCs secretome has a key role in cell-to-cell communication and has been proven to be an active mediator of immune-modulation and regeneration both in vitro and in vivo. Moreover, the use of secretome has key advantages over cell-based therapies, such as a lower immunogenicity and easy production, handling and storage. Importantly, MSCs can be modulated to alter their secretome composition to better suit specific therapeutic goals, thus, opening a large number of possibilities. Altogether these advantages now place MSCs secretome at the center of an important number of investigations in different clinical contexts, enabling rapid scientific progress in this field.

Keywords: Mesenchymal stem cells; Secretome; Soluble factors; Extra-cellular vesicles; Exosomes; Bone regeneration

Core Tip: Mesenchymal stem cells (MSCs) produce a high number of bioactive molecules and extracellular vesicles, known as secretome, which exerts important paracrine effects on neighbouring cells and tissues. The use of MSCs secretome in tissue regeneration therapies would circumvent the problems linked to MSCs-based therapies, such as low cell survival and engraftment, which importantly limit their therapeutic efficacy, or the negative side effects associated with the administration of these cells.