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World J Gastroenterol. May 7, 2021; 27(17): 1905-1919
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1905
Mesenchymal stromal cell secretome in liver failure: Perspectives on COVID-19 infection treatment
Cinzia Maria Chinnici, Giovanna Russelli, Matteo Bulati, Vitale Miceli, Alessia Gallo, Rosalia Busà, Rosaria Tinnirello, Pier Giulio Conaldi, Gioacchin Iannolo
Cinzia Maria Chinnici, Giovanna Russelli, Matteo Bulati, Vitale Miceli, Alessia Gallo, Rosalia Busà, Pier Giulio Conaldi, Gioacchin Iannolo, Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
Cinzia Maria Chinnici, Department of Regenerative Medicine, Fondazione Ri.MED, Palermo 90127, Italy
Rosaria Tinnirello, Neuroscience Unit, CNR Institute of Biomedicine and Molecular Immunology, Palermo 90146, Italy
Author contributions: Chinnici CM, Russelli G, Bulati M, Miceli V, Gallo A, Busà R, Tinnirello R, Conaldi PG and Iannolo G conducted the research and edited all drafts of the manuscript.
Supported by UPMC International, Pittsburg, United States, No. I0000026; Italian Ministry of Education, University and Research, Rome, Italy, No. CTN01_00177_888744; and PO FESR Sicilia 2014/2020 Azione 1.1.5 Project (Prometeo), No. 08PA8610200270.
Conflict-of-interest statement: The authors declare having no conflicts 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: Gioacchin Iannolo, PhD, Research Scientist, Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Via Ernesto Tricomi, 5, Palermo 90127, Italy. giannolo@ismett.edu
Received: January 27, 2021
Peer-review started: January 27, 2021
First decision: February 24, 2021
Revised: March 5, 2021
Accepted: April 5, 2021
Article in press: April 5, 2021
Published online: May 7, 2021
Processing time: 91 Days and 13.6 Hours
Abstract

Due to their immunomodulatory potential and release of trophic factors that promote healing, mesenchymal stromal cells (MSCs) are considered important players in tissue homeostasis and regeneration. MSCs have been widely used in clinical trials to treat multiple conditions associated with inflammation and tissue damage. Recent evidence suggests that most of the MSC therapeutic effects are derived from their secretome, including the extracellular vesicles, representing a promising approach in regenerative medicine application to treat organ failure as a result of inflammation/fibrosis. The recent outbreak of respiratory syndrome coronavirus, caused by the newly identified agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has forced scientists worldwide to use all available instruments to fight the infection, including the inflammatory cascade caused by this pandemic disease. The use of MSCs is a valid approach to combat organ inflammation in different compartments. In addition to the lungs, which are considered the main inflammatory target for this virus, other organs are compromised by the infection. In particular, the liver is involved in the inflammatory response to SARS-CoV-2 infection, which causes organ failure, leading to death in coronavirus disease 2019 (COVID-19) patients. We herein summarize the current implications derived from the use of MSCs and their soluble derivatives in COVID-19 treatment, and emphasize the potential of MSC-based therapy in this clinical setting.

Keywords: Mesenchymal stromal cell; COVID-19; SARS-CoV-2; Organ failure; Inflammation; Transplantation

Core Tip: The recent coronavirus disease 2019 (COVID-19) pandemic outbreak has forced scientists worldwide to use all available options to fight this disease, in particular the inflammatory cascade caused by this infection. Mesenchymal stromal cells, for their immunomodulatory potential, represent a valid approach to combat organ inflammation. The main targets for this virus are the lungs, while other organs such as the liver are compromised by the infection. Evaluation of the albumin role in COVID-19 patients, and the connection to the “capillary leak syndrome” have focused attention on liver dysfunction correlated with the infection.