Opinion Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2021; 13(12): 1813-1825
Published online Dec 26, 2021. doi: 10.4252/wjsc.v13.i12.1813
Stem cell-derived biofactors fight against coronavirus infection
Mohammadreza Ardalan, Leila Chodari, Sepideh Zununi Vahed, Seyed Mahdi Hosseiniyan Khatibi, Aziz Eftekhari, Soodabeh Davaran, Magali Cucchiarini, Leila Roshangar, Elham Ahmadian
Mohammadreza Ardalan, Sepideh Zununi Vahed, Seyed Mahdi Hosseiniyan Khatibi, Elham Ahmadian, Kidney Research Center, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
Leila Chodari, Physiology Department, Faculty of Medicine, Urmia University of Medical Sciences, Urmia 5715799313, Iran
Aziz Eftekhari, Department of Toxicology, Maragheh University of Medical Sciences, Maragheh 3453554, Iran
Soodabeh Davaran, Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
Soodabeh Davaran, Applied Drug Research Center, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
Magali Cucchiarini, Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg D-66421, Germany
Leila Roshangar, Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
Author contributions: Ahmadian E conceived and designed the study; Eftekhari A and Chodari L acquired the data; Zununi Vahed S prepared the first draft of the manuscript; Hosseiniyan Khatibi SM designed and drew the figures in the manuscript; Cucciarini M and Ardalan M proofread the manuscript and made critical revisions; Davaran S and Roshanghar L revised the manuscript; all authors read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
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: Elham Ahmadian, PhD, Assistant Professor, Kidney Research Center, Tabriz University of Medical Sciences, Golgasht Avenue, Tabriz 5166614766, Iran. ahmadian.l.h.m@gmail.com
Received: February 13, 2021
Peer-review started: February 13, 2021
First decision: April 6, 2021
Revised: April 12, 2021
Accepted: June 22, 2021
Article in press: June 22, 2021
Published online: December 26, 2021
Processing time: 314 Days and 23.8 Hours
Abstract

Despite various treatment protocols and newly recognized therapeutics, there are no effective treatment approaches against coronavirus disease. New therapeutic strategies including the use of stem cells-derived secretome as a cell-free therapy have been recommended for patients with critical illness. The pro-regenerative, pro-angiogenic, anti-inflammatory, anti-apoptotic, immunomodulatory, and trophic properties of stem cells-derived secretome, extracellular vesicles (EVs), and bioactive factors have made them suitable candidates for respiratory tract regeneration in coronavirus disease 2019 (COVID-19) patients. EVs including microvesicles and exosomes can be applied for communication at the intercellular level due to their abilities in the long-distance transfer of biological messages such as mRNAs, growth factors, transcription factors, microRNAs, and cytokines, and therefore, simulate the specifications of the parent cell, influencing target cells upon internalization and/or binding. EVs exhibit both anti-inflammatory and tolerogenic immune responses by regulation of proliferation, polarization, activation, and migration of different immune cells. Due to effective immunomodulatory and high safety including a minimum risk of immunogenicity and tumorigenicity, mesenchymal stem cell (MSC)-EVs are more preferable to MSC-based therapies. Thus, as an endogenous repair and inflammation-reducing agent, MSC-EVs could be used against COVID-19 induced morbidity and mortality after further mechanistic and preclinical/clinical investigations. This review is focused on the therapeutic perspective of the secretome of stem cells in alleviating the cytokine storm and organ injury in COVID-19 patients.

Keywords: COVID-19; Secretome; Mesenchymal stem cell; Exosome; Stem cell; Biofactors

Core Tip: The world has witnessed unbelievable damage due to the coronavirus disease 2019 (COVID-19) pandemic. The rapid propagation of the disease requires emerging therapeutic strategies. The central role of the immune system during COVID-19 highlights the importance of a balanced immune response in order to prohibit overexaggerated responses and further multiorgan dysfunction. Stem cell and stem cell-derived secretome-related therapies have gained increasing momentum in the treatment of a broad range of diseases in the past decade. In particular, the immunomodulatory properties of stem cell-derived biofactors could be a new avenue in the treatment of COVID-19 patients.