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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2019; 11(5): 270-280
Published online May 26, 2019. doi: 10.4252/wjsc.v11.i5.270
Generation of mesenchymal stem-like cells for producing extracellular vesicles
Soo Kim, Tae Min Kim
Soo Kim, Brexogen Research Center, Brexogen Inc., Seoul, Songpa-gu 05718, South Korea
Tae Min Kim, Graduate School of International Agricultural Technology and Institute of Green-Bio Science and Technology, Seoul National University, Gangwon-do, Pyeongchang 25354, South Korea
Author contributions: All authors contributed to manuscript preparation; Kim S contributed towards conception of the ideas and collecting the data; Kim TM contributed towards outlining the structure of the manuscript.
Supported by the Research Resettlement Fund for the New Faculty of Seoul National University, No. 1403-20180039.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Tae Min Kim, DVM, PhD, Assistant Professor, Graduate School of International Agricultural Technology and Institute of Green-Bio Science and Technology, Seoul National University, Pyeongchang Daero 1447, Pyeongchang, Gangwon-do 25354, South Korea. taemin21@snu.ac.kr
Telephone: +82-33-3395896 Fax: +82-33-3395547
Received: February 10, 2019
Peer-review started: February 12, 2019
First decision: March 15, 2019
Revised: April 2, 2019
Accepted: April 19, 2019
Article in press: April 19, 2019
Published online: May 26, 2019
Processing time: 104 Days and 19.5 Hours
Abstract

Mesenchymal stem cells (MSCs) are multipotent progenitor cells with therapeutic potential against autoimmune diseases, inflammation, ischemia, and metabolic disorders. Contrary to the previous conceptions, recent studies have revealed that the tissue repair and immunomodulatory functions of MSCs are largely attributed to their secretome, rather than their potential to differentiate into desired cell types. The composition of MSC secretome encompasses cytokines and growth factors, in addition to the cell-derived structures known as extracellular vesicles (EVs). EVs are membrane-enclosed nanoparticles that are capable of delivering biomolecules, and it is now believed that MSC-derived EVs are the major players that induce biological changes in the target tissues. Based on these EVs’ characteristics, the potential of EVs derived from MSC (MSC-EV) in terms of tissue regeneration and immune modulation has grown during the last decade. However, the use of MSCs for producing sufficient amount of EVs has not been satisfactory due to limitations in the cell growth and large variations among the donor cell types. In this regard, pluripotent stem cells (PSCs)-derived MSC-like cells, which can be robustly induced and expanded in vitro, have emerged as more accessible cell source that can overcome current limitations of using MSCs for EV production. In this review, we have highlighted the methods of generating MSC-like cells from PSCs and their therapeutic outcome in preclinical studies. Finally, we have also discussed future requirements for making this cell-free therapy clinically feasible.

Keywords: Mesenchymal stem cells; Extracellular vesicles; Preclinical studies; Exosomes

Core tip: The therapeutic potential of extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) has recently been reported. However, alternative MSC sources are needed to produce EVs in a quality-controlled manner. Pluripotent stem cells-derived MSC-like cells can be robustly induced in vitro, and therefore induced MSC-like cells (iMSCs) have the possibility to become an alternative source for EV production. Herein, we review current data on iMSC generation, and provide key outcomes of their therapeutic functioning in preclinical studies.