Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2020; 12(8): 731-751
Published online Aug 26, 2020. doi: 10.4252/wjsc.v12.i8.731
Mesenchymal stromal cells as potential immunomodulatory players in severe acute respiratory distress syndrome induced by SARS-CoV-2 infection
Panagiotis Mallis, Efstathios Michalopoulos, Theofanis Chatzistamatiou, Catherine Stavropoulos-Giokas
Panagiotis Mallis, Efstathios Michalopoulos, Theofanis Chatzistamatiou, Catherine Stavropoulos-Giokas, Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, Athens 11527, Greece
Author contributions: Mallis P designed and retrieved the data and prepared the whole manuscript; Michalopoulos E and Chatzistamatiou T made critical revisions related to the content of the manuscript; Stavropoulos-Giokas C performed the final approval of the manuscript.
Conflict-of-interest statement: The authors declare 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:
Corresponding author: Panagiotis Mallis, MSc, PhD, Associate Research Scientist, Teaching Assistant, Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, Athens 11527, Greece.
Received: May 15, 2020
Peer-review started: May 15, 2020
First decision: June 3, 2020
Revised: June 10, 2020
Accepted: July 19, 2020
Article in press: July 19, 2020
Published online: August 26, 2020

Severe acute respiratory syndrome coronavirus-2 and the related coronavirus disease-19 (COVID-19) is a worldwide emerging situation, which was initially reported in December 2019 in Wuhan, China. Currently, more than 7258842 new cases, and more than 411879 deaths have been reported globally. This new highly transmitted coronavirus is responsible for the development of severe acute respiratory distress syndrome. Due to this disorder, a great number of patients are hospitalized in the intensive care unit followed by connection to extracorporeal membrane oxygenation for breath supporting and survival. Severe acute respiratory distress syndrome is mostly accompanied by the secretion of proinflammatory cytokines, including interleukin (IL)-2, IL-6, IL-7, granulocyte colony-stimulating factor (GSCF), interferon-inducible protein 10 (IP10), monocyte chemotactic protein-1 (MCP1), macrophage inflammatory protein 1A (MIP1A), and tumor necrosis factor alpha (TNF-α), an event which is known as “cytokine storm”. Further disease pathology involves a generalized modulation of immune responses, leading to fatal multiorgan failure. Currently, no specific treatment or vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been developed. Mesenchymal stromal cells (MSCs), which are known for their immunosuppressive actions, could be applied as an alternative co-therapy in critically-ill COVID-19 patients. Specifically, MSCs can regulate the immune responses through the conversion of Th1 to Th2, activation of M2 macrophages, and modulation of dendritic cells maturation. These key immunoregulatory properties of MSCs may be exerted either by produced soluble factors or by cell-cell contact interactions. To date, several clinical trials have been registered to assess the safety, efficacy, and therapeutic potential of MSCs in COVID-19. Moreover, MSC treatment may be effective for the reversion of ground-glass opacity of damaged lungs and reduce the tissue fibrosis. Taking into account the multifunctional properties of MSCs, the proposed stem-cell-based therapy may be proven significantly effective in critically-ill COVID-19 patients. The current therapeutic strategy may improve the patient’s overall condition and in parallel may decrease the mortality rate of the current disease.

Keywords: SARS-CoV-2, COVID-19, Respiratory syndrome, Cytokine storm, Mesenchymal stromal cells, Immunoregulation, Lungs, Th2 response, Dendritic cells, Natural killer cells

Core tip: In this review, the therapeutic potential of mesenchymal stromal cells (MSCs) towards coronavirus disease-19 (COVID-19), will be highlighted. Importantly, MSCs exert key immunoregulatory/immunosuppressive properties that can alter significantly the immune responses. Also, MSCs share regenerative abilities, reducing in this way the lung tissue damage. These unique MSCs features, which may significantly improve the overall condition of COVID-19 patients, will be presented in the following article.